Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Endometrial CAFs Resist Effect of Antitumor Drugs In A Patient-Derived 2-Cell Hybrid Co-Culture Model

Raed Sulaiman
,
Jennifer C Aske
ORCID logo ,
Xiaoqian Lin
,
Adam Dale
,
Kris Gaster
,
Luis Rojas Espaillat
,
David Starks
,
Pradip De
,
Nandini Dey
* ORCID logo
Version 1 : Received: 20 November 2023 / Approved: 1 December 2023 / Online: 1 December 2023 (07:57:41 CET)

How to cite: Sulaiman, R.; Aske, J.C.; Lin, X.; Dale, A.; Gaster, K.; Espaillat, L.R.; Starks, D.; De, P.; Dey, N. Endometrial CAFs Resist Effect of Antitumor Drugs In A Patient-Derived 2-Cell Hybrid Co-Culture Model. Preprints 2023, 2023120054. https://doi.org/10.20944/preprints202312.0054.v1 Sulaiman, R.; Aske, J.C.; Lin, X.; Dale, A.; Gaster, K.; Espaillat, L.R.; Starks, D.; De, P.; Dey, N. Endometrial CAFs Resist Effect of Antitumor Drugs In A Patient-Derived 2-Cell Hybrid Co-Culture Model. Preprints 2023, 2023120054. https://doi.org/10.20944/preprints202312.0054.v1

Abstract

Drug resistance in tumor cells is a significant roadblock in the clinical management of advanced or recurrent diseases in endometrial cancers. As a part of the tumor-stromal ecosystem, tumor cells are ecologically connected to the cancer-associated fibroblasts (CAFs), which form contributory elements of the tumor microenvironment (TME). We recently reported a novel model of patient-derived CAF-based 2-cell Hybrid Co-Culture (HyCC) to evaluate CAFs' role in developing drug resistance and understanding personalized tumor cell-CAF dialogue. Using our 2-cell HyCC model of patient-derived endometrial CAFs, we present data to demonstrate the direct counter-inhibitory effect of CAFs to combinations of cytotoxic and targeted drugs in developing drug resistance. CAFs derived from resected endometrial tumor samples were first passage-wise characterized before and after freeze-thaw for their positive and negative CAF markers expression pattern. Paclitaxel and its combination with copanlisib, TAK228, lenvatinib, and trametinib were used to test the 3D clonogenic growth of endometrial AN3CA cells on endometrial CAFs. We demonstrate that CAF-mediated resistance to antitumor drugs occurs via direct and indirect contact with CAFs in HyCC. Our data established the strength of the 2-cell HyCC model of patient-derived CAFs in solid tumors and provided a model of resistance to antitumor drugs tailored on a patient-to-patient basis.

Keywords

Ex Vivo Resistance Platform; CAF-mediated Resistance; Combinations of cytotoxic and targeted drugs

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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