Cancer-associated fibroblasts connect metastasis-promoting communication in colorectal cancer

Abstract

Colorectal cancer (CRC) progression and eventually metastasis is directed in many aspects by a circuitous ecosystem consisting of an extracellular matrix scaffold populated by cancer-associated fibroblasts (CAFs), endothelial cells, and diverse immune cells. CAFs are recruited from local tissue-resident fibroblasts or pericryptal fibroblasts and distant fibroblast precursors. CAFs are highly abundant in CRC. In this review, we apply the metastasis-promoting communication of colorectal CAFs to 10 cancer hallmarks described by Hanahan and Weinberg. CAFs influence innate and adaptive tumor immune responses. Using datasets from previously published work, we re-explore the potential messages implicated in this process. Fibroblasts present in metastasis (metastasis-associated fibroblasts) from CRC may have other characteristics and functional roles than CAFs in the primary tumor. Since CAFs connect metastasis-promoting communication, CAF markers are potential prognostic biomarkers. CAFs and their products are possible targets for novel therapeutic strategies.

Keywords: cancer-associated fibroblasts; colorectal cancer; immune cells; metastasis; pericryptal fibroblasts.

Figure 1

Hallmarks of cancer regulated by CAFs after Hanahan and Weinberg (5).

Figure 2

Photomicrographs showing hematoxylin and eosin staining (A) and immunohistochemical staining of α-SMA (B), CD8 (C), and CD163 (D) on consecutive sections of a primary colon tumor. Scale bar is 100 μm. CC, cancer cells; S, stroma; BV, blood vessel; IC, immune cells.

Figure 3

Photomicrographs showing consecutive sections of liver metastasis of a CRC patient stained by hematoxylin and eosin (A) and stained immunohistochemically for α-SMA (B), CD8 (C), and CD163 (D). Scale bar is 100 μm. CC, cancer cells; IC, immune cells; S, stroma; H, hepatocytes.