The effect of cancer-derived soluble factors on the transformation of human mesenchymal stem cells to cancer-associated fibroblasts

Name: Htet Htet Oo, Mi Hnin

keyword: Cancer

; Mesenchymal stem cells

; Cancer-associated fibroblasts

; Soluble factors proliferation

; Migration

Abstract: Cancer has been a serious health problem and one of the leading causes of morbidity and mortality worldwide. Several recent pieces of evidence suggest that human mesenchymal stem cells (hMSCs) play an essential role in the growth and metastasis of cancer cells and affect their responses to chemotherapeutic agents and immunotherapy. hMSCs can migrate to cancer tissues and become cancer-associated fibroblasts (CAFs), which release several factors that enhance cancer growth and metastasis. Although bone marrow-derived hMSCs (BM-hMSCs) have been the common source of hMSCs for most cancer research, their harvest requires an invasive procedure and their number decreases with age. Therefore, placenta- and chorion-derived hMSCs (PL-hMSCs and CH-hMSCs), which can be obtained in large quantities by non-invasive procedures, might be used as alternative sources of hMSCs for cancer research and clinical applications. However, the effects of PL-hMSCs and CH-hMSCs on the properties of cancer cells and their ability to transform into CAFs have yet to be investigated. Our results showed that the soluble factors derived from PL-hMSCs and CH-hMSCs suppressed the proliferation and migration of the human lung adenocarcinoma cell A549, the human glioblastoma multiforme U251, the human osteosarcoma cell Saos2, and the human breast cancer cell MDA-MB231. Although soluble factors derived from A549, U251, MDA-MB231, and SaOS2 cells increased the expression levels of several CAF markers, including SA100A4, TGF1, TGF3, and SDF1 in PL-hMSCs and CH-hMSCs, these factors are insufficient to transform both hMSCs into tumor-promoting CAFs and abolish their cancer suppressive capacity. Consistent with this, the soluble factors derived from these cancer cells did not change the expression of typical hMSC surface markers of these cancer-associated hMSCs. An additional culture component, such as Matrigel, direct contact with cancer cells, and hypoxic conditions, could be included to simulate the condition in the tumor stroma to induce such a transformation. We believe that the knowledge gained from this study could improve our understanding of the interaction between cancer cells and cancer stromal cells and lead to the development of better cancer treatment in the future

Thammasat University. Thammasat University Library

Address: BANGKOK

Email: preserv@tu.ac.th

Name: Pakpoom Kheolamai

Role: advisor

Name: Chairat Tantrawatpan

Role: co-advisor

Name: Duangrat Tantikanlayaporn

Role: co-advisor

Created: 2022

Modified: 2024-07-03

Issued: 2024-07-03

DOI: 10.14457/TU.the.2022.1411

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Stem Cell Biology and Technology

Grantor: Thammasat University

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