Gene expression changes associated with high density collagen microenviroment in cancer cells

We report RNA sequencing data from 2 cancer cell line (fibrosarcoma, HT1080 and Breast cancer, MDA-MB-231) and one non-canceours cell line (human foreskin fibroblast HFF) embbeded in two different 3D collagen matrix environements. The topographical organization of collagen within the tumor ECM has been implicated in guiding cancer cell migration and independently predicts progression to metastasis. Here, we show that collagen matrices with small pores and short fibers, but not Matrigel, trigger a conserved transcriptional response and subsequent motility switch in cancer cells that results in formation of multicellular network structures. The response is not mediated by hypoxia, matrix stiffness, or bulk matrix density, but by matrix architecture and beta1 integrin upregulation. The transcriptional module associated with network formation is enriched for migration and vasculogenesis-associated genes that predicted survival in patient data across nine distinct tumor types. Evidence at the protein level of this gene module is found in patient tumors displaying a vasculogenic mimicry (VM) phenotype. Our findings link a collagen matrix-induced migration program to VM, and suggest that this process may be broadly relevant to metastatic progression in solid human cancers. Overall design: Total RNA extraction and mRNA sequencing of 3 diiferent cell lines cultured in 2 different collagen matrix conditions.