Abstract

We isolate and culture carcinoma-associated fibroblasts (CAFs) from primary tumour (CAFpt), CAFs from corresponding synchronous liver metastasis (CAFlm) as well as normal colonic fibroblasts (NCF) from the same patient. From these cultures, conditioned media (CM) was obtained. Culture of a wide panel of colorectal and pancreatic cell lines in CM from CAFlm resulted in overexpression of mRNA PRL-3 and higher overexpression in CAFs than in non-activated fibroblasts. Moreover PRL-3 mRNA expression correlates with expression of α-SMA and deposition of collagen fibrils in the stroma. We demonstrate that products secreted by CAFs trigger PRL-3 overexpression in cancer cells. Identification of these factors may contribute to new stroma-targeted therapies for desmoplastic tumours.

Highlights

  • In many epithelial tumours inclouding colorectal, the relevance of PRL-3 phosphatase to the tumorigenic process of distant dissemination is well documented [1,2,3,4,5]

  • PRL-3 is overexpressed in different colorectal and pancreatic cell lines when cultured in conditioned media derived from carcinoma-associated fibroblasts from liver metastasis We cultured a wide panel of colorectal and pancreatic cell lines, derived from primary tumours and secondary sites

  • Same trend is observed between carcinomaassociated fibroblast from primary tumour (CAFpt) and carcinoma-associated fibroblasts derived from a liver metastasis (CAFlm) (P = 0.514)

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Summary

Introduction

In many epithelial tumours inclouding colorectal, the relevance of PRL-3 phosphatase to the tumorigenic process of distant dissemination is well documented [1,2,3,4,5]. B: normalised PRL-3 mRNA expression of DLD-1 cells cultured in conditioned media (CM) derived from fibroblasts and carcinoma-associated fibroblasts. (page number not for citation purposes) http://www.molecular-cancer.com/content/8/1/46 for 24 hours in their standard culture medium (DMEMF12 + 10%FBS) or in conditioned medium obtained from CAFs derived from a CRC liver metastasis.

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Conclusion
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