Serum-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

International Journal of Cancer. Journal International Du Cancer
Aws Abdul-WahidJean Gariépy

Abstract

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 mat...Continue Reading

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Citations

Jul 3, 2019·Clinical and Translational Medicine·Tovah WilliamsonHossein Sendi
Dec 28, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yue ZhangYanfei Shen
Sep 26, 2020·Frontiers in Oncology·Carlos A Gonzalez-VillarrealElsa N Garza-Treviño
Jun 6, 2021·Journal of Cancer Research and Clinical Oncology·Susanne Schüler-ToprakOliver Treeck
Nov 29, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S Kamali ZonouziN Rezaei

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