Endocrine Abstracts

Introduction: The intricate interplay between fibroblasts and cancer cells significantly contributes to cancer invasion, extracellular matrix (ECM) modulation, and the development of drmg resistance. This study delves into understanding the specific influence of fibroblasts on Gastro-Intestinal neuroendocrine tumor (GI-NET) cell lines.

Materials and Methods: Utilizing GOT1 and COLO320 cell lines, we incorporated Normal Human Dermal Fibroblasts (NF) in our investigation. Lipophilic tracers were employed in 3D co-culture to distinguish between cell types. FAK (BI-0319) and SYK (BI1002494) kinase inhibitors, previously identified as antiproliferative on GI-NET cells, were administered. Elisa assays were conducted to quantify protein secretion levels.

Materials and Methods: The study employed the GI-NET cell lines GOT1 and COLO320, alongside Normal Human Dermal Fibroblasts (NF). A 2D invasion assay was conducted using cell inserts, followed by crystal violet staining for visualization. Cell viability assessment in 3D cultures utilized the cell-titer glow method, with fluorescent lipophilic tracers distinguishing between cell types in 3D co-culture. FAK (BI-0319) and SYK (BI1002494) kinase inhibitors, recognized for their antiproliferative effects on GI-NETs cells, were administered as drmg treatment. Protein secretion levels were quantified using Elisa.

Results: In 3D culture, fibroblasts demonstrated a partial impact on the response to FAK and SYK inhibition. In 2D invasion assay, fibroblasts strongly stimulated cancer cell invasion, yet this effect was effectively counteracted by treatment with FAK (BI-0319) and SYK (BI1002494) inhibitors. Notably, fibroblasts were observed to diminish the secretion of TIMP2, a protein recognized for its anti-invasive propertie, preventing excessive extracellular matrix (ECM) degradation and hindering tumor cell migration.

Conclusion: Although fibroblast influence on cancer cells invasion and ECM remodeling is substantial, inhibiting the focal adhesion pathway was shown to partially counteract these effects. This dual role of fibroblasts, both influencing and being influenced by FAK and SYK inhibition, underscores the complexity of their interactions in the context of cancer invasion and highlights the potential therapeutic significance of targeting these pathways.