Abstract:
:Prostate cancer (PCa) patients' mortality is mainly attributed to complications caused by metastasis of the tumor cells to organs critical for survival, such as bone. We hypothesized that PCa cell-bone interactions would promote paracrine signaling. A panel of PCa cell lines were cocultured with hydroxyapatite ([HA]; inorganic component of bone) of different densities. Conditioned media (CM) was collected and analyzed for calcium levels and effect on paracrine signaling, cell migration, and viability in vitro and in vivo. Our results showed that calcium levels were elevated in CM from cancer cell-bone cocultures, compared to media or cancer cells alone, and this could be antagonized by ethylene glycol-bis(2-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA), a calcium chelator, or knockdown of Snail protein. We also observed increased signal transducer and activator of transcription 3 (STAT3) phosphorylation and paracrine cell proliferation and migration in LNCaP cells incubated with CM from various cell lines; this phosphorylation and cell migration could be antagonized by Snail knockdown or various inhibitors including EGTA, STAT3 inhibitor (WP1066) or cathepsin L inhibitor (Z-FY-CHO). In vivo, higher HA bone density increased tumorigenicity and migration of tumor cells to HA implant. Our study shows that cancer-bone microenvironment interactions lead to calcium-STAT3 signaling, which may present an area for therapeutic targeting of metastatic PCa.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Henderson VM,Hawsawi O,Burton LJ,Campbell T,Trice K,Dougan J,Howard SM,Odero-Marah VAdoi
10.1002/mc.23019subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1349-1361issue
8eissn
0899-1987issn
1098-2744journal_volume
58pub_type
杂志文章abstract::Paclitaxel is the last choice for the treatment of advanced melanoma as a second-line chemotherapeutic agent, but there are still many cases of intrinsic resistance to paclitaxel in melanoma and the reasons that cause paclitaxel resistance remain unclear. Here, we identified that high expression of SRY-box transcripti...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23148
更新日期:2020-03-01 00:00:00
abstract::The protein EPHB4 plays a vital role in various tumor types. However, few studies into the function of circ-EPHB4 (hsa_circ_0001730) in tumors have been conducted. This study aimed to investigate the functions of circ-EPHB4 and the underlying mechanism of circ-EPHB4 in regulating hepatocellular carcinoma (HCC). The ex...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22976
更新日期:2019-06-01 00:00:00
abstract::Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 g...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22476
更新日期:2017-01-01 00:00:00
abstract::Cytokines are considered to play an important role in tumor pathogenesis and progression, and recent studies have demonstrated that a variety of forms, including interleukins (ILs) and transforming growth factor-beta(s) (TGF-beta(s)), may regulate tumors. In the present study, the expression of TGF-beta isoforms and I...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::microRNAs (miRNAs) are commonly altered in glioblastoma. Publicly available algorithms suggest the Wnt pathway is a potential target of miR-577 and the Wnt pathway is commonly altered in glioblastoma. Glioblastoma has not been previously evaluated for miR-577 expression. Glioblastoma tumors and cell lines were evaluat...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22304
更新日期:2016-05-01 00:00:00
abstract::Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell ca...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23246
更新日期:2020-10-01 00:00:00
abstract::The expression of members of the family of matrix-degrading metalloproteinases (MMPs) is believed to contribute to the complex process of invasion and metastasis. In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040617
更新日期:1991-01-01 00:00:00
abstract::Increasing evidence from recent research suggests a connection between cancer and a deranged equilibrium of histone acetylation, which is maintained by two competing enzymatic activities, histone acetyltransferases (HATs) and histone deacetylases (HDACs). It is our hypothesis that a significant proportion of leukemias...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(200004)27:4<268::aid-mc4>3
更新日期:2000-04-01 00:00:00
abstract::The levels of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) are frequently decreased in tumor cells and increased in normal cells upon treatment with ionizing radiation. We studied Mn-SOD at different stages during the neoplastic conversion of radiation-initiated Syrian hamster embryo HDR-3 cells. Mn-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199612)17:4<175::AID-MC1>3
更新日期:1996-12-01 00:00:00
abstract::We found that caffeine significantly inhibited epidermal growth factor (EGF)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in the JB6 mouse epidermal cell line. The tumor promoter-induced cell transformation was also blocked by treatment with an adenosine A1 receptor antagonist, 8-phenylt...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20120
更新日期:2005-09-01 00:00:00
abstract::Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected th...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23013
更新日期:2019-07-01 00:00:00
abstract::Transforming growth factor beta (TGFbeta) signaling has both tumor suppression and promotion roles. Smads are transcription factors that primarily mediate intracellular signaling for the TGFbeta superfamily. Loss of Smad2 and Smad4, but not Smad3 is common in human cancers. Given the complex nature of TGFbeta signalin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20336
更新日期:2007-08-01 00:00:00
abstract::Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21944
更新日期:2013-11-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connec...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20793
更新日期:2012-03-01 00:00:00
abstract::The molecular changes associated with the aging process include the reduced activity of transcription factors (such as AP-1) and an impaired response to stress, which has been well documented in the case of the heat-shock (HS) response. Using human diploid fibroblasts of early and late passages as an in vitro model fo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199609)17:1<8::AID-MC2>3.0
更新日期:1996-09-01 00:00:00
abstract::Serially transplantable rat mammary tumor (RMT) cells are not dependent on exogenous epidermal growth factor (EGF) and insulin-like growth factor-I for continuous growth in serum-free medium. Previously, we found that conditioned medium obtained from these cells contained EGF-like mitogenic activity and stimulated tyr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199602)15:2<134::AID-MC6>3
更新日期:1996-02-01 00:00:00
abstract::Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP-mix, with methylmethanesulfonate (MMS) or N'-methyl-N'-nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940110109
更新日期:1994-09-01 00:00:00
abstract::Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,meta分析
doi:10.1002/mc.20874
更新日期:2013-01-01 00:00:00
abstract::Exportin-T (XPOT) belongs to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up-regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expres...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22928
更新日期:2019-02-01 00:00:00
abstract::Nonmelanoma skin cancers (NMSCs) consist of a variety of tumor types including basal cell carcinoma, squamous cell carcinoma, a variety of hair follicle tumors, and sebaceous gland tumors. Genetic alterations that alter the fate of multipotent stem cells are believed to influence NMSC phenotype. We previously generate...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20617
更新日期:2010-04-01 00:00:00
abstract::In epithelial ovarian cancer, tumor grade is an independent prognosticator whose molecular determinants remain unknown. We investigated patterns of gene expression in well- and poorly differentiated serous papillary ovarian and peritoneal carcinomas with cDNA microarrays. A 6500-feature cDNA microarray was used for co...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10098
更新日期:2003-02-01 00:00:00
abstract::To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injectio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199711)20:3<298::aid-mc6>3
更新日期:1997-11-01 00:00:00
abstract::Centchroman (CC), a female oral contraceptive, has been shown to possess breast anti-cancer activities. Recently, we have shown CC-mediated antimetastatic effect through reversal of epithelial-to-mesenchymal transition (EMT) in breast cancer. The loss of tumor suppressor genes (TSGs) has been shown to promote EMT in b...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22424
更新日期:2016-11-01 00:00:00
abstract::Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22506
更新日期:2017-02-01 00:00:00
abstract::Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well-k...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.23183
更新日期:2020-07-01 00:00:00
abstract::Experimentally induced models of breast carcinogenesis in the rat are widely used for studying the biology of breast cancer and for developing and evaluating cancer prevention and control strategies. However, very little is known about gene expression changes that are associated with experimentally induced mammary car...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199710)20:2<204::aid-mc7>3
更新日期:1997-10-01 00:00:00
abstract::Osteosarcoma is the primary human malignant tumor affecting bone. This cancer most frequently arises in children and adolescents, with a second peak in those over the age of 50. Currently, surgery followed by radiotherapy and chemotherapy are the main treatments, but long-term positive effects are very poor. Aurora B ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22993
更新日期:2019-06-01 00:00:00
abstract::The restriction of energy intake has a profound inhibitory effect on carcinogenesis, yet the mechanism or mechanisms that account for this effect are unknown. In this experiment, the hypothesis tested was that energy restriction upregulates the expression of p27/kip1, a gene product associated with cell-cycle growth a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199904)24:4<241::aid-mc1>3
更新日期:1999-04-01 00:00:00
abstract::High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050412
更新日期:1992-01-01 00:00:00
abstract::The knowledge about the role of calcium-regulated pathways in cancer cell growth and differentiation could be useful for the development of new therapeutic approaches to diminish its mortality. The ATP2A genes encode for SERCA pumps, which modulate cytosolic Ca2+ concentration, regulating various cellular processes in...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22978
更新日期:2019-06-01 00:00:00