Abstract:
:Emerging evidence indicates the presence of tumor-initiating cells (TIC) or cancer stem cells in osteosarcoma. However, no study has shown specific markers to identify osteosarcoma TICs with in vivo tumor formation ability. Additionally, there has been a lack of investigations gauging the contribution of osteosarcoma TICs to metastatic and drug-resistant properties. In this study, we have identified mouse and human osteosarcoma TICs using mesenchymal stem cell markers CD117 and Stro-1. These markers were preferentially expressed in spheres and doxorubicin-resistant cells. Both mouse and human cells expressing these markers were sorted and analyzed for their abilities of tumor formation with as few as 200 cells, self-renewability, multipotency, drug resistance, metastatic potential, and enrichment of a metastasis-associated marker (CXCR4) and a drug resistance marker (ABCG2). CD117(+)Stro-1(+) cells efficiently formed serially transplantable tumors, whereas CD117(-)Stro-1(-) cells rarely initiated tumors. On orthotopic injections, CD117(+)Stro-1(+ )cell-derived tumors metastasized at a high frequency. Further, CD117(+)Stro-1(+) cells showed high invasive and drug-resistant properties and were efficiently enriched for CXCR4 (20-90%) and ABCG2 (60-90%). These results suggest possible mechanisms for the high metastatic and drug-resistant properties of osteosarcoma TICs. In summary, CD117 and Stro-1 identify osteosarcoma TICs associated with the most lethal characteristics of the disease-metastasis and drug resistance-and these markers offer candidates for TIC-targeted drug delivery aimed at eradicating osteosarcoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Adhikari AS,Agarwal N,Wood BM,Porretta C,Ruiz B,Pochampally RR,Iwakuma Tdoi
10.1158/0008-5472.CAN-09-3463subject
Has Abstractpub_date
2010-06-01 00:00:00pages
4602-12issue
11eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-3463journal_volume
70pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The p75 and p110 isoforms of the CUX1 homeodomain protein are overexpressed in breast tumors and cancer cell lines. To assess and compare the ability of these short CUX1 isoforms in driving mammary tumor development, we used site-specific transgenesis into the Hprt locus to generate transgenic mice expressing p75 or p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4899
更新日期:2009-09-15 00:00:00
abstract::Extracellular signal-regulated kinases (ERK) regulate cellular functions in response to a variety of external signals. However, the specific functions of individual ERK isoforms are largely unknown. Hence, we have investigated the specific function of ERK1 in skin homeostasis and tumorigenesis in ERK1 knockout mice. T...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3129
更新日期:2006-03-01 00:00:00
abstract::Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 con...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:10.1158/0008-5472.CAN-08-2604
更新日期:2009-04-01 00:00:00
abstract::One of the most promising new avenues for the development of more selective and efficacious cancer therapies relies on the antibody-mediated targeted delivery of bioactive agents (e.g., cytokines) to the tumor environment. The identification of quantitative differences in the expression of accessible vascular proteins...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1436
更新日期:2007-11-15 00:00:00
abstract::Proliferating cell nucleolar antigen P40 is a late G1-specific protein, which was found in a variety of human tumors (A. Chatterjee, J. W. Freeman, and H. Busch. Cancer Res., 47: 1123-1129, 1987). Two overlapping complementary DNA clones for antigen P40 were isolated by immunoscreening a lambda gt11 human expression l...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Silybin, a main component of the milk thistle of Silybum marianum, has been reported to possess anticancer activity. We investigated the effects of IdB 1016, a complex of silybin with phosphatidylcholine, on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice. The mechanisms involved...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2601
更新日期:2007-03-01 00:00:00
abstract::A transplantable mammary tumor derived from an outgrowth of nodule-like alveolar lesions induced by 7,12-dimethylbenz[a]anthracene in cultures of whole mammary gland was shown to produce a family of somatomedin-like polypeptides when cultured in vitro. Minced mammary tumor tissue as well as monolayer cultures of tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::The effect of caffeine on the expression of murine endogenous virus in mouse cells induced by radiation and chemicals was studied. Postirradiation treatment of K-BALB cells with caffeine enhanced cell killing as well as the induction of xenotropic virus after ultraviolet light irradiation. The degree of enhancement fo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
abstract::p51/p63 is a novel p53 homologue that has been shown to act as a transcriptional activator through the p53-binding sequence of the p21/WAF1 promoter and to induce apoptosis when it is expressed transiently in a human tumor cell line. We developed transcription assay systems for these two related genes in both Saccharo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-06-15 00:00:00
abstract::Previously, we have shown that the expression of Wnt-1-induced signaling protein-2 (WISP-2), also known as CCN5, can be regulated by multiple stimulants in estrogen receptor (ER)-positive breast tumor cells to exert their mitogenic action in these cells. Here, we show that insulin-like growth factor-1 (IGF-1), a stron...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3753
更新日期:2007-02-15 00:00:00
abstract::Sixteen clones (RASK-1 to -16) of murine monoclonal antibodies were raised against ras Mr 21,000 protein (p21). The p21 produced by Escherichia coli with inserted v-Ki-ras genes was used as immunogen. RASK-1 was found to be specific for Ki-ras p21, whereas RASK-2 to -16 reacted with the p21s of Ki-, N-, and Ha-ras gen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Lipotropes (choline, methionine, folic acid, and vitamin B12) are required for normal metabolic function at the cellular and subcellular levels. Deficiencies of any or all of them to a point of influence on methyl group metabolism has a profound effect on synthesis of cellular macromolecules and on cell proliferation....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Incidence of the loss of heterozygosity on chromosome 3p was evaluated using 7 polymorphic probes in 35 Japanese patients with sporadic renal cell carcinoma (RCC). Overall frequency of the loss of heterozygosity on 3p was 53%, representing 16 of 30 informative cases. Examination of the relationship between histopathol...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Mechanism, in addition to protein kinase C activation may mediate 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated differentiation of leukemic cells. We compared the effect of pretreating intact monoblastoid U937 cells with TPA or the diacylglycerol derivative, 1-oleoyl-2-acetylglycerol (OAG), by studying the pro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Despite considerable efforts to improve early detection of ovarian cancer, the majority of women at time of diagnosis will have metastatic disease. Understanding and targeting the molecular underpinnings of metastasis continues to be the principal challenge in the clinical management of ovarian cancer. Whereas the mul...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3676
更新日期:2006-02-15 00:00:00
abstract::Four new human non-small cell lung cancer cell lines have been established in vitro. These cell lines have been characterized by (a) growth of a tumor in nude mice with histopathology similar to that of the primary, (b) isoenzyme patterns phenotypically human and distinct from each other, (c) distinguishing karyotypic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::A purse-string suture was put into the rat's cecum to form a "diverticulum." When the thread cut this stitch, the resultant extensive necrotic zone healed for a long time. The presence of a foreign body (ligature) provided a permanent source of injury to the cecal mucosa. The lesions caused an increase in [3H]thymidin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::Aberrant epidermal growth factor receptor (EGFR) signaling is a major cause of tumor progression and metastasis; the underlying mechanisms, however, are not well understood. In particular, it remains elusive whether deregulated EGFR pathway is involved in epithelial-mesenchymal transition (EMT), an early event that oc...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0575
更新日期:2007-10-01 00:00:00
abstract::The pharmacodynamic parameters of 1-beta-D-arabinofuranosylcytosine (ara-C) in patient plasma and its active anabolite 1-beta-D-arabinofuranosylcytosine-5-triphosphate (ara-CTP) in circulating and bone marrow blast cells were studied in 20 pediatric patients with acute leukemia. ara-C (3 g/m2) was administered as a sh...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-15 00:00:00
abstract::Different cell growth effects were observed in MCF-7 cells after six daily exposures to either 17 beta-estradiol (E2), 2-hydroxyestradiol (2-OHE2), or 2-methoxyestradiol (2-MeOE2) at 10 nM levels. 2-OHE2 enhanced cell growth significantly (P < 0.05) more than did the parent compound, whereas 2-MeOE2 inhibited cell gro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::The regulation of urokinase secretion and receptor display in a well-differentiated colon carcinoma cell line, GEO, adapted to serum-free conditions was examined. In protein-free medium, the cell line secreted 0.8 +/- 0.1 ng/ml/10(6) cells of urokinase in a 3-day period as determined by an enzyme-linked immunosorbent ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-15 00:00:00
abstract::p21(Cip1) is a cyclin-dependent kinase inhibitor whose abundance increases in cells exposed to radiation or other DNA-damaging agents. Such increases activate a G1 checkpoint, which allows time for DNA repair before S phase entry. By inhibiting cell cycle progression, p21(Cip1) potentially suppresses tumorigenesis, an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-06-15 00:00:00
abstract::A stable phenol, gamma-L-glutaminyl-4-hydroxybenzene (GHB), is oxidized by tyrosinase in the gill tissues of the mushroom Agaricus bisporus to a quinone and a second oxidation product which together suppress mitochondrial energy production and the synthesis of proteins and nucleic acids in the zygote, thus establishin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-04-01 00:00:00
abstract::The i.p. inoculation of C3H mice with 5 times 10-6 cells of a transplantable ovarian carcinoma invariably evokes accumulation of large amounts of ascitic fluid. Histological and pharmacotherapeutic studies indicate that obstruction to peritoneal lymphatic drainage is a key factor in the formation of carcinomatous asci...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-02-01 00:00:00
abstract::Abnormalities of chromosome 1, including trisomy for all or a portion of the long arm, have been frequently reported in many cancers. Anomalies of chromosome 19 are far less common, although a t(1;19)(q23;p13) translocation has been reported in association with pre-B-cell leukemia. We have observed a t(1;19)(q12;p13) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::An epitope region, located at amino acid residues 173-180 (EAAA-GIQW), of a human cell proliferation-associated nucleolar antigen, P120, has been defined by mutational analysis and competition assays. A synthetic peptide corresponding to this epitope region completely blocks the binding of the anti-P120 antibody to Es...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::Loss of susceptibility to apoptosis signals is a crucial step in carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a promising therapeutic strategy. c-Jun-N-terminal-kinases (JNK) have been implicated in stress-induced apoptosis, but may also contribute to survival signaling. Here we show that CD...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-2618
更新日期:2005-08-01 00:00:00
abstract::Ras associated with diabetes (Rad) is a Ras-related GTPase that promotes cell growth by accelerating cell cycle transitions. Rad knockdown induced cell cycle arrest and premature senescence without additional cellular stress in multiple cancer cell lines, indicating that Rad expression might be critical for the cell c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3791
更新日期:2010-06-01 00:00:00
abstract::Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in huma...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3821
更新日期:2009-04-15 00:00:00
abstract::The mammary carcinoma cell line MFM-223 is characterized by high androgen and low estrogen and progesterone receptor levels. With the dextran charcoal method, androgen binding was determined at 160 fmol/mg protein corresponding to approximately 100,000 binding sites per cell in whole cell binding assays. The estrogen ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00