Cancer‐associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients

Abstract

Tumor epithelial cells within a tumor coexist with a complex microenvironment in which a variety of interactions between its various components determine the behavior of the primary tumors. Cancer- associated fibroblasts (CAF) and M2 macrophages, characterized by high expression of different markers, including a-SMA, FSP1 and FAP, or CD163 and DCSIGN, respectively, are involved in the malignancy of different tumors. In the present study, expression of the above markers in CAF and M2 macrophages was analyzed using RT-PCR and immunohistochemistry in the normal mucosa and tumor tissue from a cohort of 289 colorectal cancer patients. Expression of CAF and M2 markers is associated with the clinical outcome of colorectal cancer patients. Moreover, the combination of CAF and M2 markers identifies three groups of patients with clear differences in the progression of the disease. This combined variable could be a decisive factor in the survival of advanced-stage patients. Taken together, these analyses demonstrate the prognostic involvement of interrelationships between DCSIGN, CD163, a-SMA, FSP1 and FAP markers in the survival of colon cancer patients.This work has been supported by Fundación Científica AECC, SAF2010-20750, S2010 ⁄BMD-2344, RTICC-RD06 ⁄ 0020 ⁄ 0020, PI12 ⁄ 02037 and Fundación Banco Santander. A.G.H. laboratory was supported by RD06 ⁄ 0020 ⁄ 0040. C.P. is the recipient of a Miguel Servet Contract from the Instituto de Salud Carlos III (CP09 ⁄ 00294) and V.G. is the recipient of a Fundación Científica AECC fellowshi

Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression

“…Because a variety of microenvironmental factors are involved in the progression of human cancer, synergistic or additive effects of Girdin phosphorylation with those factors may be important for clinical outcome of the patients. In addition, the gene-expression profiles of CAF in individual cancers need to be considered (19)(20)(21)(22)(23). Therefore, future studies should concentrate on determining the importance of Akt-Girdin signaling in the tumor microenvironment for the evaluation of clinical outcomes of the patients with various stages of malignant tumors on an individualized basis.…”

“…CAF physically assist in the invasion of surrounding tissue by actively remodeling the ECM, subsequently providing routes that can be exploited by tumor cells (14,18). On the basis of these findings, CAF gene-expression assays have been developed as useful prognostic indicators in recent clinical studies (19)(20)(21)(22)(23). Clearly, it is important to dissect the mechanisms mediating the localization, proliferation, and activity of CAF, as such insights may lead to the development of novel therapies that target the tumor microenvironment (24).…”

Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma

“…The abundance of CAFs has been clinically correlated with poor prognosis in several malignancies, including lung [6] and colorectal cancers [7]. CAFs produce various cytokines and growth factors, such as transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8, and insulin-like growth factor (IGF), and directly or indirectly influence the behavior of malignant cells through signaling pathways mediated by these molecules [8,9].…”

Immunotherapy in the treatment of colorectal cancer: a new kid on the block

“…They secrete tumour-promoting factors that contribute to tumor invasion and neoangiogenesis [14] . CAFs play a critical role in CRC immunosuppression, particularly in CRC RAS mutated; in fact they lead to tumour progression by activating epithelial mesenchymal transition and TGF-beta/SMAD signalling [15] : high levels of CAFs markers are correlated with poor prognosis in CRC [16] . [7] .…”