Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression

DeRosa, Chad; Furusato, Bungo; Shaheduzzaman, Syed; Srikantan, Vasantha; Wang, Z; Chen, Y; Siefert, Mary Lou; Ravindranath, Lakshmi; Young, Denise; Nau, Marion M.; Dobi, Albert; Werner, Thomas; McLeod, David G.; Vahey, Maryanne; Sesterhenn, Isabell A.; Srivastava, Shiv; Petrovics, György

doi:10.1038/pcan.2011.61

Cited by 60 publications

(47 citation statements)

References 39 publications

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“…LCM derived normal and malignant prostate epithelial cells were obtained from OCT embedded frozen sections as described previously 40 - 43 . Briefly, specimens obtained immediately after surgical resection of prostate, were OCT embedded and frozen on glass slides placed on dry ice.…”

Section: Methodsmentioning

confidence: 99%

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Methylation of thePMEPA1gene, a negative regulator of the androgen receptor in prostate cancer

et al. 2014

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The prostate transmembrane protein androgen induced 1 (PMEPA1) gene is highly expressed in prostate epithelial cells and is a direct transcriptional target for the androgen receptor (AR). AR protein levels are controlled by the AR-PMEPA1 negative feedback loop through NEDD4-E3 ligase. Reduced expression of PMEPA1 observed in prostate tumors, suggests that loss of PMEPA1 may play critical roles in prostate tumorigenesis. This study focuses on epigenetic mechanisms of reduced PMEPA1 expression in the cancer of the prostate (CaP). Benign (n = 77) and matched malignant (n = 77) prostate epithelial cells were laser capture micro-dissected from optimum cutting temperature embedded frozen prostate sections from 42 Caucasian American (CA) and 35 African American (AA) cases. Purified DNA specimens were analyzed for CpG methylation of the PMEPA1 gene. PMEPA1 mRNA expression levels were evaluated by qRT-PCR. Analysis of PMEPA1 methylation and mRNA expression in the same tumor cell populations indicated a significant inverse correlation between mRNA expression and methylation in CaP (P = 0.0115). We noted higher frequency of CpG methylation within the evaluated first intronic region of the PMEPA1 gene in prostate tumors of CA men as compared with AA. In CaP cell lines, PMEPA1 expression was induced and AR protein levels were diminished in response to treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (decitabine). Cell culture-based studies demonstrated that decitabine restores PMEPA1 expression in AR-positive CaP cell lines. This report reveals the potential role of PMEPA1 gene methylation in the regulation of AR stability. Thus, downregulation of PMEPA1 may result in increased AR protein levels and function in CaP cells, contributing to prostate tumorigenesis.

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Section: Methodsmentioning

confidence: 99%

“…TaqMan qRT-PCR using RNA from LCM derived tumor and normal epithelial cells was performed as described previously 40 - 43 . The expression of GAPDH as the RNA input control and the target gene expression were simultaneously analyzed for each sample (in duplicates).…”

Section: Methodsmentioning

confidence: 99%

Methylation of thePMEPA1gene, a negative regulator of the androgen receptor in prostate cancer

et al. 2014

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“…Among other functions, SPARC participates both in carcinoma EMT and in TAFs' myofibroblastic differentiation, thus promoting both tumorigenesis and desmoplasia (55). In prostate cancer, for example, the expression of SPARC by malignant cells can be predictive of metastasis, while in pancreatic and nonsmall cell lung cancers, elevated expression of SPARC at the tumor stroma indicates poor prognostics (29,74,189). Regarding SPARC's tumorsuppressing effects in breast, ovarian, colon, and bladder carcinomas, SPARC has been associated with inhibition of proliferation and induction of apoptosis (55, 309).…”

Section: Osteonectin/sparcmentioning

confidence: 99%

The wound healing, chronic fibrosis, and cancer progression triad

Rybinski

Franco‐Barraza

Cukierman

2014

Physiological Genomics

209

175

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For decades tumors have been recognized as “wounds that do not heal.” Besides the commonalities that tumors and wounded tissues share, the process of wound healing also portrays similar characteristics with chronic fibrosis. In this review, we suggest a tight interrelationship, which is governed as a concurrence of cellular and microenvironmental reactivity among wound healing, chronic fibrosis, and cancer development/progression (i.e., the WHFC triad). It is clear that the same cell types, as well as soluble and matrix elements that drive wound healing (including regeneration) via distinct signaling pathways, also fuel chronic fibrosis and tumor progression. Hence, here we review the relationship between fibrosis and cancer through the lens of wound healing.

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“…Prostate cancer cell expression of ON increases in metastatic sites compared the primary tumor [113]. ON expression is also associated with decreased E-cadherin and increased N-cadherin expression in melanoma cells and is increased in less differentiated breast and prostate cancer cells, suggesting a role in epithelial-mesenchymal transition (EMT) [114, 115]. In contrast, some researchers report that ON has either no effect or antagonistic effects on tumor progression, even in these same cancer types [116, 117].…”

Section: Osteonectin (On)mentioning

confidence: 99%

Matricellular proteins as regulators of cancer metastasis to bone

Trotter

Yang

2016

Matrix Biology

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Metastasis is the major cause of the death in cancer patients, and a frequent site of metastasis for many cancers is the bone marrow. Therefore, understanding the mechanisms underlying the metastatic process is necessary for future prevention and treatment. The tumor microenvironment is now known to play a role in the metastatic cascade, both at the primary tumor and in metastatic sites, and includes both cellular and non-cellular components. The extracellular matrix (ECM) provides structural support and signaling cues to cells. One particular group of molecules associated with the ECM, known as matricellular proteins, modulate multiple aspects of tumor biology, including growth, migration, invasion, angiogenesis and metastasis. These proteins are also important for normal function in the bone by regulating bone formation and bone resorption. Recent studies have described a link between some of these proteins and metastasis of various tumors to the bone. The aim of this review is to summarize what is currently known about matricellular protein influence on bone metastasis. Particular attention to the contribution of both tumor cells and non-malignant cells in the bone has been given.

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Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression

Cited by 60 publications

References 39 publications

Methylation of thePMEPA1gene, a negative regulator of the androgen receptor in prostate cancer

Methylation of thePMEPA1gene, a negative regulator of the androgen receptor in prostate cancer

The wound healing, chronic fibrosis, and cancer progression triad

Matricellular proteins as regulators of cancer metastasis to bone

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