Soluble Endoglin (sCD105) as a Novel Biomarker for Detecting Aggressive Prostate Cancer

Vidal, Adriana C.; Duong, Frank; Howard, Lauren E.; Wiggins, Emily; Freedland, Stephen J.; Bhowmick, Neil A.; Gong, Jun

doi:10.21873/anticanres.14088

Cited by 12 publications

(12 citation statements)

References 14 publications

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“…Endoglin shedding has also been shown to suppress tumor angiogenesis. Indeed, low soluble endoglin is associated with aggressive prostate cancer, whereas elevated soluble endoglin is associated with recurrence‐free survival in patients 100,101 …”

Section: Tgf‐β Superfamily Co‐receptors and Their Role In Cancermentioning

confidence: 99%

“…Indeed, low soluble endoglin is associated with aggressive prostate cancer, whereas elevated soluble endoglin is associated with recurrence-free survival in patients. 100,101 While endoglin is primarily expressed in the tumor vasculature, recent studies have identified a role for endoglin in cancer cells and other tumor-associated cell types. 102 For example, when expressed in cancer cells, endoglin is associated with cancer progression in endometrial cancer, ovarian cancer, hepatocellular carcinoma, Ewing sarcoma, and melanoma.…”

Section: Cancermentioning

confidence: 99%

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TGF‐β superfamily co‐receptors in cancer

Pawlak

Blobe

2021

Developmental Dynamics

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Transforming growth factor‐β (TGF‐β) superfamily signaling via their cognate receptors is frequently modified by TGF‐β superfamily co‐receptors. Signaling through SMAD‐mediated pathways may be enhanced or depressed depending on the specific co‐receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co‐receptors from the membrane to generate soluble forms that are often antagonistic to the membrane‐bound receptors. The co‐receptors discussed here include TβRIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto‐1, MuSK, and RGMs. Dysregulation of these co‐receptors can lead to altered TGF‐β superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF‐β superfamily co‐receptors on TGF‐β superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co‐receptors.

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Section: Tgf‐β Superfamily Co‐receptors and Their Role In Cancermentioning

confidence: 99%

Section: Cancermentioning

confidence: 99%

TGF‐β superfamily co‐receptors in cancer

Pawlak

Blobe

2021

Developmental Dynamics

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“…Similar to THY1, ENG + ASPN + fibroblasts were also elevated in cribriform prostate cancer. Both ENG and ASPN are associated with adverse outcomes and may promote the progression of aggressive prostate cancer [32,[49][50][51]. While the overall expression of NT5E, TNC, and PDGFRβ did not change in the tumor microenvironment, ASPN expression was altered in these cells.…”

mentioning

confidence: 95%

“…Similar to FAP, Thy-1 cell surface antigen (THY1) is also overexpressed in prostate CAFs [47], and it may have a role in regulating cancer stem cells [48]. Endoglin (ENG) is another CAF marker associated with adverse outcomes, and it has been shown to promote castration-resistant prostate cancer [49][50][51]. Tenascin C (TNC), 5'-nucleotidase ecto (NT5E), and platelet-derived growth factor receptor beta (PDGFRβ) are other CAF markers that are currently candidate targets for imaging or therapeutics [52][53][54][55].…”

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confidence: 99%

A distinct repertoire of cancer‐associated fibroblasts is enriched in cribriform prostate cancer

Hesterberg

Rios

Wolf

et al. 2021

The Journal of Pathology CR

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Outcomes for men with localized prostate cancer vary widely, with some men effectively managed without treatment on active surveillance, while other men rapidly progress to metastatic disease despite curative-intent therapies. One of the strongest prognostic indicators of outcome is grade groups based on the Gleason grading system. Gleason grade 4 prostate cancer with cribriform morphology is associated with adverse outcomes and can be utilized clinically to improve risk stratification. The underpinnings of disease aggressiveness associated with cribriform architecture are not fully understood. Most studies have focused on genetic and molecular alterations in cribriform tumor cells; however, less is known about the tumor microenvironment in cribriform prostate cancer. Cancer-associated fibroblasts (CAFs) are a heterogeneous population of fibroblasts in the tumor microenvironment that impact cancer aggressiveness. The overall goal of this study was to determine if cribriform prostate cancers are associated with a unique repertoire of CAFs. Radical prostatectomy whole-tissue sections were analyzed for the expression of fibroblast markers (ASPN in combination with FAP, THY1, ENG, NT5E, TNC, and PDGFRβ) in stroma adjacent to benign glands and in Gleason grade 3, Gleason grade 4 cribriform, and Gleason grade 4 noncribriform prostate cancer by RNAscope ® . Halo ® Software was used to quantify percent positive stromal cells and expression per positive cell. The fibroblast subtypes enriched in prostate cancer were highly heterogeneous. Both overlapping and distinct populations of low abundant fibroblast subtypes in benign prostate stroma were enriched in Gleason grade 4 prostate cancer with cribriform morphology compared to Gleason grade 4 prostate cancer with noncribriform morphology and Gleason grade 3 prostate cancer. In addition, gene expression was distinctly altered in CAF subtypes adjacent to cribriform prostate cancer. Overall, these studies suggest that cribriform prostate cancer has a unique tumor microenvironment that may distinguish it from other Gleason grade 4 morphologies and lower Gleason grades.

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“…is involved in TGF-β1 induced cell signal transduction (1,(32)(33)(34)(35). Although, the intracellular mechanisms by which and how CD105 modulates TGF-β1 signalling have been extensively studied, they need further clarification (7,9,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46).…”

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confidence: 99%

CD105 (Endoglin): A Potential Anticancer Therapeutic Inhibits Mitogenesis and Map Kinase Pathway Activation

et al. 2021

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Background: CD105 is highly expressed on human activated endothelial cells (ECs), is an important component of the TGF-β1 receptor complex and is essential for angiogenesis. CD105 expression is up-regulated in activated ECs and is an important potential marker for cancer prognosis. Materials and Methods: In vitro rat myoblasts transfected with the L-CD105 and S-CD105 transfectants. The transfectants were treated with TGF-β1 for the angiogenesis study. Results: L-CD105 affects cell proliferation in the presence and absence of TGF-β1, and inhibits p-ERK1/2, p-MEK1/2 and p-c-Jun in L-CD105 transfectants compared to controls. The induction of phospho-ERK1/2 following treatment with TGF-β1 remained significantly lower in L-CD105 transfectants compared to controls. Conclusion: L-CD105 inhibits the phosphorylation of ERK1/2, MEK1/2, c-Jun1/2/3, and associated signalling intermediates. CD105 modulates cell growth and TGF-β1 induced cell signalling through ERK-c-Jun expression. CD105 (Endoglin) is a 180-kDa homodimeric integral transmembrane glycoprotein composed of disulphide-linked 90-95 kDa subunits and is a receptor component for TGF-β1 and TGF-β3 (1, 2). It is primarily found on activated angiogenic endothelial cells (ECs) of microvessels of cancer and numerous other angiogenic diseases (3-8). CD105 regulates a wide range of cellular and physiological responses, including embryonic development, homoeostasis, wound healing, chemotaxis, cell proliferation, differentiation, adhesion, migration, and apoptosis (4, 9-11). Overexpression of CD105 modulates TGF-β signalling by interacting with TGF-β receptor I (TGF-β RI) and/or TGFβ receptor II (TGF-β RII) on CD105 transfected L6E9 cells and human vascular smooth muscle cells through mitogenactivated protein kinases (MAPKs) (12, 13) and smallmothers-against-decapentaplegic (Smad) proteins (14, 15). Since CD105 overexpression was previously shown to be a marker of poor cancer outcome (16), and the phosphorylated ERK is a potential predictor of sensitivity to the treatment of carcinoma, as shown by various in vitro studies (17, 18), thus CD105 could be used as a potential therapy in cancer. Currently, CD105 is under phase 1 and phase 2 clinical trial in cancer patients (our and Seon et al.'s unpublished data). CD105 has two isoforms, long-form L-CD105 and shortform S-CD105 (19), both of which bind to TGF-β1 and TGF-β3. These two isoforms have contrasting roles in angiogenesis with L-CD105 being pro-angiogenic and S-CD105 inhibiting angiogenesis (20). Since L-CD105 is expressed at a markedly higher level than S-CD105 in ECs, the overall balance tends towards a pro-angiogenic phenotype in vivo (21). The expression of CD105 on ECs and other cells is upregulated by both TGF-β and hypoxia (22), but their additive effect is substantially greater than by themselves (23). Vascular lesions (telangiectasia and arteriovenous malformations) in CD105 haploinsufficient hereditary hemorrhagic telangiectasia type I (HHT1) patients are associated with a loss of the capillary network (1, 24). T...

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Soluble Endoglin (sCD105) as a Novel Biomarker for Detecting Aggressive Prostate Cancer

Cited by 12 publications

References 14 publications

TGF‐β superfamily co‐receptors in cancer

TGF‐β superfamily co‐receptors in cancer

A distinct repertoire of cancer‐associated fibroblasts is enriched in cribriform prostate cancer

CD105 (Endoglin): A Potential Anticancer Therapeutic Inhibits Mitogenesis and Map Kinase Pathway Activation

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