Graded hypoxia modulates the invasive potential of HT1080 fibrosarcoma and MDA MB231 carcinoma cells.


:Spatial and temporal oxygen heterogeneity exists in most solid tumour microenvironments due to an inadequate vascular network supplying a dense population of tumour cells. An imbalance between oxygen supply and demand leads to hypoxia within a significant proportion of a tumour, which has been correlated to the likelihood of metastatic dissemination in both rodent tumour models and human patients. Experimentally, it has been demonstrated that near-anoxic in vitro exposure results in transiently increased metastatic potential in some tumour cell lines. The purpose of this study was to examine the effect of graded low oxygen conditions on the invasive phenotype of human tumour cells using an in vitro model of basement membrane invasion, in which we measured oxygen availability directly at the invasion surface of the transwell chamber. Our results show a relationship between culture vessel geometry and time to achieve hypoxia which may affect the interpretation of low oxygen experiments. We exposed the human tumour cell lines, HT1080 and MDA MB231, to graded normobaric oxygen (5% O(2)-0.2% O(2)) either during or prior to in vitro basement membrane invasion to simulate conditions of intravasation and extravasation. A secondary aim was to investigate the potential regulation of matrix metalloproteinase activity by oxygen availability. We identified significant reductions in invasive ability under low oxygen conditions for the HT1080 cell line and an increase in invasion at intermediate oxygen conditions for the MDA MB231 cell line. There were differences in the absolute activity of the individual matrix metalloproteinases, MMP-2, -9, -14, between the two cell lines, however there were no significant changes following exposure to hypoxic conditions. This study demonstrates cell line specific effects of graded oxygen levels on invasive potential and suggests that intermediate levels of low oxygen may increase metastatic dissemination.


Clin Exp Metastasis


Subarsky P,Hill RP




Has Abstract


2008-01-01 00:00:00












  • Role of the beta1-integrin subunit in the adhesion, extravasation and migration of T24 human bladder carcinoma cells.

    abstract::The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell-cell and cell-matrix interactions. We investigated the role of integrin subunits in ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Heyder C,Gloria-Maercker E,Hatzmann W,Niggemann B,Zänker KS,Dittmar T

    更新日期:2005-01-01 00:00:00

  • The lack of correlation between experimental metastatic potential and platelet aggregating activity of B16 melanoma clones viewed in relation to tumor cell heterogeneity.

    abstract::Two widely used B16 melanoma cell lines of low and high lung colonizing potential (B16-F1 and B16-F10) were compared in their ability to induce platelet aggregation. The results of these experiments showed a reproducible difference in platelet aggregating activity of these two cell lines which directly correlated with...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kimura AK,Mehta P,Xiang JH,Lawson D,Dugger D,Kao KJ,Lee-Ambrose L

    更新日期:1987-04-01 00:00:00

  • Comparative study on Lewis lung tumour lines with 'low' and 'high' metastatic capacity. III. Glycosaminoglycan synthesis, transport and degradation in cell lines.

    abstract::The glycosaminoglycans (GAGs) of low (LM) and highly metastatic (HM) cell lines of the Lewis lung tumour (3LL) were compared using [3H]glucosamine labelling techniques. The GAGs isolated from nuclei, cytoplasm, pericellular fractions and medium were analysed by cellulose acetate electrophoresis and by digestion with s...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Pogány G,Moczar E,Jeney A,Timár J,Timár F,Ditrói K,Lapis K

    更新日期:1989-11-01 00:00:00

  • Platelet-endothelial cell adhesion molecule-1 (CD31) redistributes from the endothelial junction and is not required for the transendothelial migration of melanoma cells.

    abstract::We have examined the role of platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) during the transendothelial migration of melanoma cells using a novel in vitro system. Comparable studies have suggested the involvement of PECAM-1 in leukocyte transendothelial migration. Such studies have been confirmed using i...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Voura EB,Chen N,Siu CH

    更新日期:2000-01-01 00:00:00

  • TGF-beta specifically enhances the metastatic attributes of murine lung adenocarcinoma: implications for human non-small cell lung cancer.

    abstract::Lung cancer is the most frequent and one of the most deadly cancer types and is classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Transforming growth factor beta (TGFβ) regulates a wide array of cell functions and plays a major role in lung diseases, including NSCLC. TGFβ signals through t...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Vázquez PF,Carlini MJ,Daroqui MC,Colombo L,Dalurzo ML,Smith DE,Grasselli J,Pallotta MG,Ehrlich M,Bal de Kier Joffé ED,Puricelli L

    更新日期:2013-12-01 00:00:00

  • The efficacy of Tilmanocept in sentinel lymph mode mapping and identification in breast cancer patients: a comparative review and meta-analysis of the ⁹⁹mTc-labeled nanocolloid human serum albumin standard of care.

    abstract::Sentinel lymph node (SLN) mapping is common, however question remains as to what the ideal imaging agent is and how such an agent might provide reliable and stable localization of SLNs. (99m)Tc-labeled nanocolloid human serum albumin (Nanocoll) is the most commonly used radio-labeled colloid in Europe and remains the ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,meta分析,评审


    authors: Tokin CA,Cope FO,Metz WL,Blue MS,Potter BM,Abbruzzese BC,Hartman RD,Joy MT,King DW,Christman LA,Vera DR,Wallace AM

    更新日期:2012-10-01 00:00:00

  • The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma.

    abstract::High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to cont...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Cipollone JA,Graves ML,Köbel M,Kalloger SE,Poon T,Gilks CB,McNagny KM,Roskelley CD

    更新日期:2012-03-01 00:00:00

  • Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer cells: enhancement of their invasive behavior partly dependant on αv integrins.

    abstract::At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence. The presence of ascites, which acts as a dynamic reservoir of active molecules and cellular components, correlates with the OC peritoneal metastasis and is associated with poor pro...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Carduner L,Leroy-Dudal J,Picot CR,Gallet O,Carreiras F,Kellouche S

    更新日期:2014-08-01 00:00:00

  • Novel hyperthermia for metastatic bone tumors with magnetic materials by generating an alternating electromagnetic field.

    abstract::We have developed a novel hyperthermic treatment modality using magnetic materials for metastatic bone tumors. The purpose of this study is to show the results of novel hyperthermia for metastatic bone tumors. This novel hyperthermic treatment modality was used for 15 patients with 16 metastatic bone lesions. In seven...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Matsumine A,Kusuzaki K,Matsubara T,Shintani K,Satonaka H,Wakabayashi T,Miyazaki S,Morita K,Takegami K,Uchida A

    更新日期:2007-01-01 00:00:00

  • GPR56 plays varying roles in endogenous cancer progression.

    abstract::GPR56, a non-classical adhesion receptor, was previously reported to suppress tumor growth and metastasis in xenograft models using human melanoma cell lines. To understand whether GPR56 plays similar roles in the development of endogenous tumors, we analyzed cancer progression in Gpr56 (-/-) mice using a variety of t...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Xu L,Begum S,Barry M,Crowley D,Yang L,Bronson RT,Hynes RO

    更新日期:2010-04-01 00:00:00

  • BRMS1 contributes to the negative regulation of uPA gene expression through recruitment of HDAC1 to the NF-kappaB binding site of the uPA promoter.

    abstract::The BRMS1 metastasis suppressor was recently shown to negatively regulate NF-kappaB signaling and down regulate NF-kappaB-dependent uPA expression. Here we confirm that BRMS1 expression correlates with reduced NF-kappaB DNA binding activity in independently derived human melanoma C8161.9 cells stably expressing BRMS1....

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Cicek M,Fukuyama R,Cicek MS,Sizemore S,Welch DR,Sizemore N,Casey G

    更新日期:2009-01-01 00:00:00

  • Bladder metastasis from renal cell carcinoma: retrospective analysis of 65 reported cases.

    abstract::This study was carried out to clarify the presentation, treatment options, and prognosis of renal cell carcinoma (RCC) metastasis to the bladder in which we do not yet have a comprehensive understanding. A systematic Medline, Web of Science, Embase, Google, and Ichushi Web search was performed to identify articles des...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Matsumoto K,Hayakawa N,Nakamura S,Oya M

    更新日期:2015-02-01 00:00:00

  • An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells.

    abstract::Tumor cells exposed to a growth stress such as low pH, glucose starvation and hypoxia have been shown to exhibit a transient increase in experimental metastatic potential, particularly when allowed to recover under normal growth conditions for a period of 24-48 h. In this study we examined whether this increase in met...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Jang A,Hill RP

    更新日期:1997-09-01 00:00:00

  • MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial-mesenchymal transition traits.

    abstract::We have investigated the gelatinase profiles and invasiveness of clonal tumour sublines derived from a spontaneously arising mammary tumour in a Balb/cfC3H mouse. The 67NR. 66c14 and 4T1.2 sublines have low, intermediate and high metastatic potential respectively. In Boyden chamber studies, Matrigel invasion was seen ...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Tester AM,Ruangpanit N,Anderson RL,Thompson EW

    更新日期:2000-01-01 00:00:00

  • Radiobiology and radiotherapy of brain metastases.

    abstract::Brain metastases are the most common intracranial tumors in adults, accounting for more than 50% of all such cases. The approach to and management of brain metastases have evolved significantly in recent years due to several reasons. These include advances in neurosurgical and radiotherapeutic techniques, improved sys...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Thiagarajan A,Yamada Y

    更新日期:2017-10-01 00:00:00

  • Sialylation of E-cadherin does not change the spontaneous or ET-18-OMe-mediated aggregation of MCF-7 human breast cancer cells.

    abstract::We have investigated the role of sialylation on cell-cell adhesion mediated by E-cadherin. Two MCF-7 human breast cancer cell variants were studied: MCF-7/AZ cells showed a spontaneous cell-cell adhesion in the fast and slow aggregation assay. whereas the adhesion deficient MCF-7/6 cell variant failed to form larger a...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Steelant WF,Recchi MA,Noë VT,Boilly-Marer Y,Bruyneel EA,Verbert A,Mareel MM,Delannoy P

    更新日期:1999-05-01 00:00:00

  • Combined effect of dehydroxymethylepoxyquinomicin and gemcitabine in a mouse model of liver metastasis of pancreatic cancer.

    abstract::Activation of nuclear factor-κB (NF-κB) has been implicated in metastasis of pancreatic cancer. We investigated the effects of the novel NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on the inhibition of liver metastasis of pancreatic cancer in a mouse model of clinical liver metastasis. Nude mice were xenogr...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Suzuki K,Aiura K,Matsuda S,Itano O,Takeuchi O,Umezawa K,Kitagawa Y

    更新日期:2013-04-01 00:00:00

  • IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.

    abstract::The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of I...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Herzberg F,Schöning M,Schirner M,Topp M,Thiel E,Kreuser ED

    更新日期:1996-03-01 00:00:00

  • Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors.

    abstract::The growth and metastatic behavior of three human tumor cell lines and a human colon carcinoma previously passaged in vivo were compared between nude mice and scid mice after xenotransplantation. The three human tumor lines included a bladder carcinoma (T24B), a melanoma (RPMI 7931) and a lacZ gene-transduced breast c...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Xie X,Brünner N,Jensen G,Albrectsen J,Gotthardsen B,Rygaard J

    更新日期:1992-05-01 00:00:00

  • Transcriptional regulation of osteopontin and the metastatic phenotype: evidence for a Ras-activated enhancer in the human OPN promoter.

    abstract::Elevated osteopontin (OPN) transcription often correlates with increased metastatic potential of transformed cells, and in several model systems OPN--whether produced by the tumor cells or by stromal cells - has been shown to enhance metastatic ability. Sequence elements in the OPN promoter have been identified on the...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Denhardt DT,Mistretta D,Chambers AF,Krishna S,Porter JF,Raghuram S,Rittling SR

    更新日期:2003-01-01 00:00:00

  • A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells.

    abstract::A new model for the study of spontaneous bone metastasis has been developed which allows for the quantification of metastatic tumor burden and cancer cell growth rate, and which describes the progressive changes in bone morphology. Walker 256 (W256) cells or vehicle were injected into the left upper thigh muscle of ma...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Kostenuik PJ,Singh G,Suyama KL,Orr FW

    更新日期:1992-11-01 00:00:00

  • A convenient clinically relevant model of human breast cancer bone metastasis.

    abstract::Breast cancer patients with advanced disease exhibit bone metastases, leading to the formation of osteolytic lesions for which the only currently available treatments are palliative. Here, we describe how we refined a mouse model of human breast cancer metastasis into bone, characterized its transcriptome and demonstr...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Garcia T,Jackson A,Bachelier R,Clément-Lacroix P,Baron R,Clézardin P,Pujuguet P

    更新日期:2008-01-01 00:00:00

  • Isolation and characterization of a low metastatic variant from EL-4 mouse T-lymphoma.

    abstract::A variant cell line (EL-4ad) which adhered to a tissue culture dish was isolated from highly metastatic EL-4 murine T-lymphoma. The experimental and spontaneous metastatic ability of EL-4ad was lower than that of the EL-4 parent cell line. The cell surface phenotypes of both cell lines were CD2+3+4-8-45+TCR alpha beta...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Ota T,Tanino M,Kohno H,Funamoto H,Odashima S

    更新日期:1992-09-01 00:00:00

  • The role of intraperitoneal chemotherapy in the surgical management of pancreatic ductal adenocarcinoma: a systematic review.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remain...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Brind'Amour A,Webb M,Parapini M,Sidéris L,Segedi M,Chung SW,Chartier-Plante S,Dubé P,Scudamore CH,Kim PTW

    更新日期:2021-01-24 00:00:00

  • Metastasis of mammary tumours in mice: relationship with morphology of primary tumour, and reproductive background of host.

    abstract::The lungs of BR6 breeding female mice which had developed spontaneous mammary tumours, were examined histologically for the presence of metastases. Metastatic nodules, or tumour cell emboli within blood vessels, were found in the lungs of 3 out of 42 (7 per cent) mice with pregnancy-dependent tumours, and in 33 out of...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Lee AE,Pang LS,Rogers LA,Jeffery RE

    更新日期:1983-07-01 00:00:00

  • Role of simvastatin in tumor lymphangiogenesis and lymph node metastasis.

    abstract::Lymphangiogenesis plays a crucial role in promoting cancer metastasis to sentinel lymph nodes (LNs) and beyond. Increasing data have shown that simvastatin, a cholesterol-lowering medication for the prevention of cardiovascular diseases, is involved in tumor growth and dissemination, and endothelial functions. This st...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Ji RC,Eshita Y,Kobayashi T,Hidano S,Kamiyama N,Onishi Y

    更新日期:2018-12-01 00:00:00

  • Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer.

    abstract::Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin or BM-40) is a glycoprotein component of the extracellular matrix that has been reported to be involved with a variety of cellular processes. Although SPARC expression levels are frequently altered in a variety of tumor types, the exact im...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Wong SY,Crowley D,Bronson RT,Hynes RO

    更新日期:2008-01-01 00:00:00

  • Selective antimetastatic effect of heparins in preclinical human melanoma models is based on inhibition of migration and microvascular arrest.

    abstract::Use of heparin derivatives in several cancer types revealed that anticoagulant therapies have a beneficiary side effect: delay of tumor progression. Since there are no data on human melanoma, we have analyzed the effect of heparins in preclinical models. Neither unfractionated heparin (UFH), nor its low molecular weig...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Bereczky B,Gilly R,Rásó E,Vágó A,Tímár J,Tóvári J

    更新日期:2005-01-01 00:00:00

  • Intracellular esterase activity in living cells may distinguish between metastatic and tumor-free lymph nodes.

    abstract:BACKGROUND:One of the major clinical problems in breast cancer detection is the relatively high incidence of occult lymph node metastases undetectable by standard procedures. Since the ascertainment of breast cancer stage determines the following treatment, such a "hypo-diagnosis" leads to inadequate therapy, and hence...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章


    authors: Afrimzon E,Deutsch A,Shafran Y,Zurgil N,Sandbank J,Pappo I,Deutsch M

    更新日期:2008-01-01 00:00:00

  • Multiple pathways of cell invasion are regulated by multiple families of serine proteases.

    abstract::The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that co...

    journal_title:Clinical & experimental metastasis

    pub_type: 杂志文章,评审


    authors: Del Rosso M,Fibbi G,Pucci M,D'Alessio S,Del Rosso A,Magnelli L,Chiarugi V

    更新日期:2002-01-01 00:00:00