The roles of collagens and fibroblasts in cancer

A hallmark of cancerous and fibrotic diseases is disruption of tissue microarchitecture and associated organ fibrosis or tumor fibrosis (desmoplasia). The fibrotic response is characterized by excessive turnover, deposition, post-translational modification, and architectural remodeling of the extracellular matrix driven primarily by altered fibroblast activity, chronic inflammation, and angiogenesis. This typically leads to increased collagen production and cross-linking and altered degradation of the collagenous matrix. This results in the loss of correct tissue organization and aberrant cellular behavior, release of matrix-bound growth factors, and unmasking of cryptic sites on collagens with potent signaling activity. All these collagen alterations drive disease progression and can affect treatment response. Tools to detect these remodeling events could be used as biomarkers of a specific fibrotic, angiogenic, or inflammatory signature. Here, we introduce some of the important roles that collagens and collagen remodeling play in cancer and touch on potential biomarkers for use in the clinic.