Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer

Ni, Weidong; Yang, Zheng; Cui, Chunzhi; Cui, Yan; Fang, Lijing; Xuan, Yanhua

doi:10.1016/j.bbrc.2017.03.021

Cited by 75 publications

(72 citation statements)

References 16 publications

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“…In terms of clinical progression, the TNC-low group in the total number of cases and among the high stage (pT ≥3) cases showed worse prognosis in terms of local recurrence/ metastasis. This finding is in contrast to the study of Ni et al, showing that high levels of TNC is significantly linked to lymph node metastasis and clinical stage [31] but in agreement with another study which reported weak TNC expression in high grade PCa [30]. No low risk cases or metastasis tissues were used in our study, and we focused on TNC-producing cells not overall TNC expression in the matrix.…”

Section: Discussionsupporting

confidence: 85%

Stroma transcriptomic and proteomic profile of prostate cancer metastasis xenograft models reveals conservation of bone microenvironment signatures

Karkampouna

Filippo

et al. 2020

Preprint

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Prostate cancer (PCa) is the second leading cause of cancer-associated death in men with therapy resistance acquisition to androgen deprivation treatment and metastasis progression.Understanding the mechanisms of tumor progression to metastatic stage is necessary for the design of therapeutic and prognostic schemes. The main objective of the current study is to determine, using transcriptomic and proteomic analyses on patient derived-xenograft models, whether differentially aggressive PCa tumors predispose their microenvironment (stroma) to a metastatic gene expression pattern, and how this information could be applied in prognostics.Transcriptomic profiling (RNA Sequencing) was performed on PCa PDX models representing different disease stages; BM18 (androgen dependent bone metastasis) and LAPC9 (androgen independent bone metastasis). Using organism-specific reference databases, the humanspecific transcriptome, representing the tumor, was identified and separated from the mousespecific transcriptome (representing the contributing stroma counterpart) from the same PDX tumor samples. To identify proteome changes in the tumor (human) versus the stroma (mouse), we performed human and mouse cell separation using the MACS mouse depletion sorting kit, and subjected protein lysates to quantitative TMT labeling and mass spectrometry. We show

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Section: Discussionsupporting

confidence: 85%

Stroma transcriptomic and proteomic profile of prostate cancer metastasis xenograft models reveals conservation of bone microenvironment signatures

Karkampouna

Filippo

et al. 2020

Preprint

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“…Immuno-blot analysis was performed as previously described. 4 Cells were collected and lysed with protease inhibitors. Equal amounts of proteins was loaded on SDS-PAGE gels and then transferred to a PVDF membrane.…”

Section: Western Blottingmentioning

confidence: 99%

“…1,2 Metastasis is a high-risk complication and the major cause of death in patients with PCa. 3,4 Androgen deprivation therapy remains the primary clinical treatment for patients in the early stages of PCa. As the disease develops into castration-resistant PCa, almost all patients with advanced PCa will experience recurrence and distal organ metastasis.…”

Section: Introductionmentioning

confidence: 99%

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Piao¹,

Li²,

Feng³

et al. 2020

CMAR

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The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression. Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffinembedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting. Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells. Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.

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“…In addition, higher expression of tenascin C (a potential stromal marker of prostate cancer progression; ref. 14) and coexpression of aSMA and vimentin (marker of myofibroblast conversion; ref. 5), were observed in AA compared with EA ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, we also noticed increased IHC expression of the extracellular matrix (ECM) protein; tenascin-C in AA patients. High tenascin-C found in CAF have been reported to be associated with poor prognosis in prostate cancer (14). Interestingly, increased tenascin-C is found in keloid disease that affects dark-skinned patients and has been described for its inability to restrain the wound-healing process similar to reactive stroma in the TME (36).…”

Section: Discussionmentioning

confidence: 99%

Elevation of Stromal-Derived Mediators of Inflammation Promote Prostate Cancer Progression in African-American Men

Gillard

Javier

et al. 2018

Cancer Research

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Progress in prostate cancer racial disparity research has been hampered by a lack of appropriate research tools and better understanding of the tumor biology. Recent gene expression studies suggest that the tumor microenvironment (TME) may contribute to racially disparate clinical outcomes in prostate cancer. Analysis of the prostate TME has shown increased reactive stroma associated with chronic inflammatory infiltrates in African-American (AA) compared with European-American (EA) patients with prostate cancer. To better understand stromal drivers of changes in TME, we isolated prostate fibroblasts (PrF) from AA (PrF) and EA (PrF) prostate cancer tissues and studied their functional characteristics. PrF showed increased growth response to androgens FGF2 and platelet-derived growth factor. Compared with PrF, conditioned media from PrF significantly enhanced the proliferation and motility of prostate cancer cell lines. Expression of markers associated with myofibroblast activation (αSMA, vimentin, and tenascin-C) was elevated in PrF tumorigenicity of an AA patient-derived prostatic epithelial cell line E006AA was significantly increased in the presence of PrF compared with PrF, and RNA-seq data and cytokine array analysis identified a panel of potential proinflammatory paracrine mediators (BDNF, CHI3L1, DPPIV, FGF7, IL18BP, IL6, and VEGF) to be enriched in PrF E006AA cell lines showed increased responsiveness to BDNF ligand compared with EA-derived LNCaP and C4-2B cells. Addition of a TrkB-specific antagonist significantly reduced the protumorigenic effects induced by PrF compared with PrF These findings suggest that fibroblasts in the TME of AA patients may contribute to the health disparity observed in the incidence and progression of prostate cancer tumors. These findings suggest that stromal cells in the tumor microenvironment of African-American men promote progression of prostate cancer by increasing levels of a specific set of pro-inflammatory molecules compared with European-American men. http://cancerres.aacrjournals.org/content/canres/78/21/6134/F1.large.jpg .

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Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer

Cited by 75 publications

References 16 publications

Stroma transcriptomic and proteomic profile of prostate cancer metastasis xenograft models reveals conservation of bone microenvironment signatures

Stroma transcriptomic and proteomic profile of prostate cancer metastasis xenograft models reveals conservation of bone microenvironment signatures

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Elevation of Stromal-Derived Mediators of Inflammation Promote Prostate Cancer Progression in African-American Men

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