Inflammatory Role of Cancer-Associated Fibroblasts in Invasive Breast Tumors Revealed Using a Fibrous Polymer Scaffold

Balachander, Gowri Manohari and Talukdar, Pinku Mani and Debnath, Monojit and Rangarajan, Annapoorni and Chatterjee, Kaushik (2018) Inflammatory Role of Cancer-Associated Fibroblasts in Invasive Breast Tumors Revealed Using a Fibrous Polymer Scaffold. In: ACS APPLIED MATERIALS & INTERFACES, 10 (40). pp. 33814-33826.

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Abstract

Inflammation in cancer fuels metastasis and worsens prognosis. Cancer-associated fibroblasts (CAFs) present in the tumor stroma play a vital role in mediating the cascade of cancer inflammation that drives metastasis by enhancing angiogenesis, tissue remodeling, and invasion. In vitro models that faithfully recapitulate CAF-mediated inflammation independent of coculturing with cancer cells are nonexistent. We have engineered fibrous matrices of poly(epsilon-caprolactone) (PCL) that can maintain the manifold tumor-promoting properties of patient-derived CAFs, which would otherwise require repetitive isolation and complex coculturing with cancer cells. On these fibrous matrices, CAFs proliferated and remodeled the extracellular matrix (ECM) in a parallel-patterned manner mimicking the ECM of high-grade breast tumors and induced sternness in breast cancer cells. The response of the fibroblasts was observed to be sensitive to the scaffold architecture and not the polymer composition. The CAFs cultured on fibrous matrices exhibited increased activation of the NF-kappa B pathway and downstream proinflammatory gene expression compared to CAFs cultured on conventional two-dimensional (2D) dishes and secreted higher levels of proinflammatory cytokines such as IL-6, GM-CSF, and MIP-3 alpha. Consistent with this, we observed increased infiltration of inflammatory cells to the tumor site and enhanced invasiveness of the tumor in vivo when tumor cells were injected admixed with CAFs grown on fibrous matrices. These data suggest that CAFs better retain their tumor-promoting proinflammatory properties on fibrous polymeric matrices, which could serve as a unique model to investigate the mechanisms of stroma-induced inflammation in cancer progression.

Item Type:	Journal Article
Publication:	ACS APPLIED MATERIALS & INTERFACES
Publisher:	AMER CHEMICAL SOC
Additional Information:	Copy right for this article belong to AMER CHEMICAL SOC
Keywords:	tissue scaffolds; breast cancer; electrospinning; inflammation; cancer-associated fibroblasts; NF-kappa B pathway
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Mechanical Sciences > Materials Engineering (formerly Metallurgy)
Date Deposited:	29 Oct 2018 15:31
Last Modified:	29 Oct 2018 15:31
URI:	http://eprints.iisc.ac.in/id/eprint/60987

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