Reverse of non-small cell lung cancer drug resistance induced by cancer associated fibroblasts via a paracrine pathway

Abstract

Tumor microenvironment orchestrates the sustained growth, metastasis and recurrence of cancer. As an indispensable component of tumor microenvironment, cancer associated fibroblasts (CAFs) are considered as an essential synthetic machine producing various tumor components, leading to cancer sustained stemness, drug resistance and tumor recurrence. Here, we developed a sustainable primary culture of lung cancer cells fed with lung cancer associated fibroblasts, resulting in enrichment and acquisition of drug resistance in cancer cells. Moreover, IGF2/AKT/Sox2/ABCB1 signaling activation in cancer cells was observed in the presence of cancer associated fibroblasts, which induce P-glycoprotein (P-GP) up-regulated expression and the drug resistance of non-small cell lung cancer cells. Our results demonstrated that cancer associated fibroblast cells constitute a supporting niche for cancer drug resistance acquisition. Thus, traditional chemotherapy combined with IGF2 signaling inhibitor may present an innovative therapeutic strategy for non-small cell lung cancer therapy.

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