Expression of extracellular matrix proteins: tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma

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Abstract

Introduction:

The interchanged stromal-epithelial relations and altered expression profiles of various extracellular matrix (ECM) proteins creates a suitable microenvironment for cancer development and growth. We support the opinion that remodeling of the extracellular matrix plays an important role in the cancer progression. The aim of this study was to examine the expression of ECM proteins tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma.

Methods:

Glands and surrounding stroma were analyzed in randomly selected specimens from 52 patients with prostate cancer and 28 patients with benign prostatic hyperplasia (BHP). To evaluate the intensity of tenascin-C, fibronectin and galectin-3 expression the percentage of positively immunostained stromal cells was examined.

Results:

Compared to BPH, stroma of prostatic adenocarcinoma showed statistically significant increase in tenascin-C expression (p < 0.001), predominantly around neoplastic glands, while fibronectin (p = 0.001) and galectin-3 (p < 0.001) expression in the same area was decreased.

Conclusions:

Our study confirms changes in the expression of ECM proteins of prostate cancer which may have important role in the cancer development.

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Most cited references 20

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A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis

Nathan Reticker-Flynn, David F. Braga Malta, Monte Winslow … (2012)

Extracellular matrix interactions play essential roles in normal physiology and many pathological processes. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Here we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. Using a genetic mouse model of lung adenocarcinoma, we measure the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of the adhesion profiles differentiates metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. We show that these molecules correlate with human disease and that their interactions are mediated in part by α3β1 integrin. Thus, our platform allowed us to interrogate interactions between metastatic cells and their microenvironments, and identified ECM and integrin interactions that could serve as therapeutic targets.

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Decreased galectin-3 expression in prostate cancer.

R A Pacis, M J Pilat, K J Pienta … (2000)

Galectin-3 is a carbohydrate-binding protein whose level of expression has been shown to be correlated with metastatic potential in a number of different tumor types. The purpose of this investigation was to examine galectin-3 expression in several tumorigenic and nontumorigenic prostate cell lines and prostate tissue samples. The expression of galectin-3 in cell lines and tissue samples was evaluated by tissue immunohistochemistry and Western blot analysis. Human cell lines PC-3M, PC-3, DU-145, PrEC-1, and MCF10A demonstrated the presence of galectin-3. Galectin-3 was not detected in TSU-pr1 and LNCaP by Western blot analysis. We furthered our studies by examining a series of human prostate tissue samples for expression of galectin-3. Overall, approximately 60-70% of the normal tissue examined demonstrated heterogenous expression of galectin-3. In stage II tumors, however, there was a dramatic decrease in galectin-3 expression in both PIN and tumor sections, with only 10.5% (2/19) of these samples expressing this protein. Stage III tumors also demonstrated a decreased expression of galectin-3, although this downregulation was not as dramatic, with 35% of PIN samples and 52% of tumor tissue expressing galectin-3 (P < 0.01). These data demonstrate that galectin-3 is downregulated in prostate cancer. The altered downregulation pattern of galectin-3 observed between tumor stages suggests different roles for galectin-3 in the progression of prostate cancer. Copyright 2000 Wiley-Liss, Inc.

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Stretching Fibroblasts Remodels Fibronectin and Alters Cancer Cell Migration

Mingfang Ao, Bryson Brewer, Lijie Yang … (2015)

Most investigations of cancer-stroma interactions have focused on biochemical signaling effects, with much less attention being paid to biophysical factors. In this study, we investigated the role of mechanical stimuli on human prostatic fibroblasts using a microfluidic platform that was adapted for our experiments and further developed for both repeatable performance among multiple assays and for compatibility with high-resolution confocal microscopy. Results show that mechanical stretching of normal tissue-associated fibroblasts (NAFs) alters the structure of secreted fibronectin. Specifically, unstretched NAFs deposit and assemble fibronectin in a random, mesh-like arrangement, while stretched NAFs produce matrix with a more organized, linearly aligned structure. Moreover, the stretched NAFs exhibited an enhanced capability for directing co-cultured cancer cell migration in a persistent manner. Furthermore, we show that stretching NAFs triggers complex biochemical signaling events through the observation of increased expression of platelet derived growth factor receptor α (PDGFRα). A comparison of these behaviors with those of cancer-associated fibroblasts (CAFs) indicates that the observed phenotypes of stretched NAFs are similar to those associated with CAFs, suggesting that mechanical stress is a critical factor in NAF activation and CAF genesis.

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Author and article information

Journal

Journal ID (publisher-id): JHS

Title: Journal of Health Sciences

Publisher: University of Sarajevo Faculty of Health Studies (Bosnia )

ISSN (Print): 2232-7576

ISSN (Electronic): 1986-8049

Publication date (Print): 2015

Volume: 5

Issue: 3

Pages: 72-77

Affiliations

[1 ]Ljudevit Jurak Department of Pathology, Sestre milosrdnice University Hospital Center, Zagreb, Croatia

[2 ]Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia

[3 ]Department of Urology, Sestre milosrdnice University Hospital Center, Zagreb, Croatia

Author notes

[* ]Corresponding Author: Monika Ulamec, Ljudevit Jurak Department of Pathology, Sestre milosrdnice Clinical Hospital Center, Vinogradska cesta 29, 10000 Zagreb, Croatia. Phone: +385 1 37 87 602; Fax: +385 1 37 87 244, E-mail: monika.ulamec@ 123456kbcsm.hr

Article

Publisher ID: JHS-5-72

DOI: 10.17532/jhsci.2015.314

SO-VID: 85cccb26-afdb-45ac-8c22-e8f9f51a625b

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Expression of extracellular matrix proteins: tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma

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Abstract

Introduction:

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Conclusions:

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Journal of Health Sciences

Most cited references 20

A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis

Decreased galectin-3 expression in prostate cancer.

Stretching Fibroblasts Remodels Fibronectin and Alters Cancer Cell Migration

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