Three-Dimensional Collagen Type I Matrix Up-Regulates Nuclear Isoforms of the Microtubule Associated Protein Tau Implicated in Resistance to Paclitaxel Therapy in Ovarian Carcinoma

Abstract

Epithelial ovarian carcinoma is the deadliest gynecologic malignancy. One reason underlying treatment failure is resistance to paclitaxel. Expression of the microtubule associated protein tau has recently been proposed as a predictor of response to paclitaxel in ovarian carcinoma patients. Expression of tau was probed using immunohistochemistry in 312 specimens of primary, and 40 specimens of metastatic, ovarian carcinoma. Serous epithelial ovarian carcinoma cell line models were used to determine the expression of tau by Western blot and immunofluorescence staining. Subcellular fractionation and Western blot were employed to examine nuclear and cytoplasmic localization of tau. Gene silencing and clonogenic assays were used to evaluate paclitaxel response. Tau was expressed in 44% of all tested cases. Among the primary serous epithelial ovarian carcinoma cases, 46% were tau-positive. Among the metastatic serous epithelial ovarian carcinomas, 63% were tau-positive. Cell culture experiments demonstrated that tau was expressed in multiple isoforms. Three-dimensional collagen I matrix culture conditions resulted in up-regulation of tau protein. Silencing of tau with specific siRNAs in a combination with three-dimensional culture conditions led to a significant decrease of the clonogenic ability of cells treated with paclitaxel. The data suggest that reduction of tau expression may sensitize ovarian carcinoma to the paclitaxel treatment.

Marine Collagen Substrates for 2D and 3D Ovarian Cancer Cell Systems

“…Normal ovarian tissue has a specific collagen signature characterized by thin, long wavy fibrils, parallel to the epithelial boundary, while, during cancer progression collagen organization facilitates cancer cell migration by creating a net of thick and short fibrils, usually perpendicular to the epithelial/cancer growing boundary, known as Tumor-Associated Collagen Signature (TACS-3) (Adur et al, 2014;Cho et al, 2015). Collagen remodeling and physical reorganization not only exert a pro-migratory function but are also associated with chemoresistance (Gurler et al, 2015).…”

The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma

“…In PDAC, type I collagen promotes cancer cell invasion, migration and drug resistance [20–26]. Furthermore, type I collagen can promote an immature cellular phenotype similar to CSCs in colorectal cancer [27].…”

Functional role of the Tau protein in epithelial ovarian cancer cells

“…Accordingly, there is the need to research Tau protein level expression in other cell types. One study compared the level of Tau protein expression among five types of serous OC cells 16. The level of Tau protein expression was different in each type 16.…”

“…One study compared the level of Tau protein expression among five types of serous OC cells 16. The level of Tau protein expression was different in each type 16. The reason for the difference in Tau protein expression among the histological types or among individuals is unclear 16.…”

“…16 The reason for the difference in Tau protein expression among the histological types or among individuals is unclear. 16 Other research reported that repeated sequences, CpG islands, and haplotypes affect the DNA and RNA levels of MAPT and regulate MAPT gene expression. 17 These factors might have different actions among the cells of each histological type.…”