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S erum‐derived carcinoembryonic antigen ( CEA ) activates fibroblasts to induce a local re‐modeling of the extracellular matrix that favors the engraftment of CEA ‐expressing tumor cells
Author(s) -
AbdulWahid Aws,
Cydzik Marzena,
Fischer Nicholas W.,
Prodeus Aaron,
Shively John E,
Martel Anne,
Alminawi Samira,
Ghorab Zeina,
Berinstein Neil L.,
Gariépy Jean
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31586
Subject(s) - carcinoembryonic antigen , extracellular matrix , cancer research , metastasis , fibronectin , fibroblast , paracrine signalling , cancer , biology , immunology , medicine , cell culture , microbiology and biotechnology , receptor , genetics
Elevated levels of the carcinoembryonic antigen (CEA; CEACAM5) in the serum of colorectal cancer (CRC) patients represent a clinical biomarker that correlates with disease recurrence. However, a mechanistic role for soluble CEA (sCEA) in tumor progression and metastasis remains to be established. In our study, we report that sCEA acts as a paracrine factor, activating human fibroblasts by signaling through both the STAT3 and AKT1‐mTORC1 pathways, promoting their transition to a cancer‐associated fibroblast (CaF) phenotype. sCEA‐activated fibroblasts express and secrete higher levels of fibronectin, including cellular EDA + ‐fibronectin (Fn‐EDA) that selectively promote the implantation and adherence of CEA‐expressing cancer cells. Immunohistochemical analyses of liver tissues derived from CRC patients with elevated levels of sCEA reveal that the expression of cellular Fn‐EDA co‐registers with CEA‐expressing liver metastases. Taken together, these findings indicate a direct role for sCEA as a human fibroblast activation factor, in priming target tissues for the engraftment of CEA‐expressing cancer cells, through the differentiation of tissue‐resident fibroblasts, resulting in a local change in composition of the extracellular matrix.