Collagen and fibronectin coatings shape pancreatic cancer cell growth and drug response in vitro

Pancreatic cancer remains one of the hardest malignancies to treat, and much of that difficulty has been traced to the tumor microenvironment, the dense web of non-cancerous cells and molecules that surrounds tumor cells. A new study published in BMC Cancer examined two extracellular matrix proteins produced by pancreatic stellate cells, collagen type I and fibronectin, to determine how each affects the behavior of pancreatic cancer cells in the laboratory. The findings show that these two matrix components act in distinctly different ways, with collagen type I largely suppressing cell growth while fibronectin tends to support it, and both altering how the cells respond to standard chemotherapy drugs.

The research team, led by Manoj Amrutkar, Anette Vefferstad Finstadsveen, Caroline S. Verbeke and Ivar P. Gladhaug, used six pancreatic cancer cell lines for their experiments. Three of these were primary lines established in-house, designated PCC-1, PCC-2 and PCC-7, while the other three were well-known immortalized lines: BxPC-3, Mia PaCa-2 and Panc-1. Each line was grown on laboratory surfaces coated with either collagen type I or fibronectin, or was exposed to conditioned medium collected from pancreatic stellate cells, which served as a control condition reflecting the broader secretory output of these stromal cells.

Using functional assays, the investigators measured changes in cell growth, adhesion, colony formation, migration and chemosensitivity. The results revealed considerable heterogeneity across the six cell lines, but a clear pattern emerged: collagen type I coating predominantly inhibited growth, whereas fibronectin coating was predominantly growth-permissive. This divergence suggests that the specific composition of the extracellular matrix, rather than simply the presence of stromal proteins, may determine whether tumor cells are pushed toward proliferation or restraint.

Colony formation, a measure of the ability of individual cells to establish expanding clusters, was suppressed by collagen type I coating but not by fibronectin. Migration showed a different profile. Increased movement was observed in three of the six cell lines after exposure to collagen type I coating, while conditioned medium from pancreatic stellate cells stimulated migration in five of the six lines. This indicates that the full complement of factors secreted by stellate cells has a broader pro-migratory reach than either matrix protein alone.

Perhaps most consequential for treatment were the chemosensitivity results. Exposure to collagen type I coating, fibronectin coating, or stellate cell conditioned medium all reduced the sensitivity of pancreatic cancer cells to gemcitabine and 5-fluorouracil, two chemotherapeutic agents commonly used against this disease. Fibronectin coating produced the maximum observed reduction in sensitivity to gemcitabine, while collagen type I coating produced the maximum reduction in sensitivity to 5-fluorouracil. These findings align with the long-standing observation that pancreatic tumors show profound resistance to chemotherapy, a resistance thought to be driven in large part by the complex tumor microenvironment.

To understand what stellate cells contribute beyond the two matrix proteins studied directly, the team analyzed the proteomic profile of the conditioned medium using mass spectrometry. This analysis revealed an abundance of proteins related to extracellular matrix organization, glycometabolic regulation and cancer cell growth. The presence of metabolic and growth-regulatory proteins alongside structural matrix components suggests that stellate cells influence tumor cells through multiple parallel pathways rather than through a single mechanism.

Immunoblotting experiments then examined how key intracellular regulators of pancreatic cancer growth changed in response to these treatments. The researchers found differentially altered levels of integrins α2β1 and α5β1, cadherins, and the phosphorylated forms of ERK and FAK across the cell lines following exposure to conditioned medium or to the collagen and fibronectin coatings. Integrins are cell-surface receptors that connect cells to their surrounding matrix, cadherins mediate cell-to-cell adhesion, and ERK and FAK are signaling proteins involved in growth and motility pathways. The differential pattern of changes across lines is consistent with the heterogeneity seen in the functional assays.

The study underscores the role of pancreatic stellate cells and their extracellular matrix products, collagen type I and fibronectin, in promoting altered growth behavior and chemosensitivity in pancreatic cancer cells. The authors conclude that the composition of the tumor microenvironment may significantly influence treatment efficacy. Because the experiments were conducted entirely in vitro using cell lines grown on coated surfaces or exposed to conditioned medium, the findings represent controlled laboratory observations rather than direct measurements in patients. The use of both primary and immortalized lines, and the noted heterogeneity among them, highlights that individual tumor contexts may respond differently to the same stromal signals.

These results add mechanistic detail to a growing body of work on why pancreatic cancer responds poorly to chemotherapy. By isolating the contributions of two major matrix proteins and comparing them with the broader secretome of stellate cells, the study provides a framework for understanding how specific microenvironmental components shape drug resistance. The identification of integrin signaling, cadherin expression and ERK and FAK phosphorylation as points of differential regulation offers potential directions for future research into targeting the stromal compartment of pancreatic tumors.

Subject of Research: Effects of collagen and fibronectin extracellular matrix coatings on pancreatic cancer cell growth, migration and chemotherapy sensitivity in vitro

Article Title: Differential effects of collagen and fibronectin coating on human primary pancreatic cancer cell behavior

Article References: Amrutkar, M., Finstadsveen, A. V., Verbeke, C. S., & Gladhaug, I. P. (2026). Differential effects of collagen and fibronectin coating on human primary pancreatic cancer cell behavior. BMC Cancer. https://doi.org/10.1186/s12885-026-17181-x

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17181-x

Keywords: pancreatic cancer, tumor microenvironment, extracellular matrix, collagen type I, fibronectin, pancreatic stellate cells, chemoresistance, gemcitabine, 5-fluorouracil, integrins, cell migration, in vitro study