Abstract

Mesenchymal stem cells (MSCs) are commonly isolated from bone marrow and adipose tissue. Depending on the tissue of origin, MSCs have different characteristics and physiological effects. In various cancer studies, MSCs have been found to have either tumor-promoting or tumor-inhibiting action. This study investigated the effect of adipose tissue-MSCs (AT-MSCs) and bone marrow-MSCs (BM-MSCs) on global long interspersed nuclear element-1 (LINE-1) methylation, the expression level of microenvironment remodeling genes and cell proliferation, migration and invasion of oral tongue squamous cell carcinoma (OTSCC). Additionally, we studied the effect of human tongue squamous carcinoma (HSC-3)-conditioned media on LINE-1 methylation and the expression of microenvironment remodeling genes in AT-MSCs and BM-MSCs. Conditioned media from HSC-3 or MSCs did not affect LINE-1 methylation level in either cancer cells or MSCs, respectively. In HSC-3 cells, no effect of MSCs-conditioned media was detected on the expression of ICAM1, ITGA3 or MMP1. On the other hand, HSC-3-conditioned media upregulated ICAM1 and MMP1 expression in both types of MSCs. Co-cultures of AT-MSCs with HSC-3 did not induce proliferation, migration or invasion of the cancer cells. In conclusion, AT-MSCs, unlike BM-MSCs, seem not to participate in oral cancer progression.

Highlights

  • Mesenchymal stem cells (MSCs) comprise a heterogeneous source of adherent cells that express specific surface markers, e.g., CD73, CD90 and CD105, and have the capacity for multilineage differentiation [1]

  • Our results demonstrated that Bone marrow-derived MSCs (BM-MSCs) were able to promote the invasion of oral tongue squamous cell carcinoma (OTSCC) cells via inducing the expression of genes linked to chemokine signaling, epithelial plasticity, cell motility and invasion [16]

  • We examined the tumorigenic potential of adipose tissue-derived MSCs (AT-MSCs) on OTSCC by evaluating the proliferation, migration and invasion of HSC-3 and dysplastic oral keratinocyte (DOK) cells

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Summary

Introduction

Mesenchymal stem cells (MSCs) comprise a heterogeneous source of adherent cells that express specific surface markers, e.g., CD73, CD90 and CD105, and have the capacity for multilineage differentiation [1]. The role of MSCs in cancer has generated interest and several studies have been carried out to that end, but the results have been controversial Some studies attribute both AT-MSCs and BM-MSCs to promoting tumor progression and metastasis [6,8,9]. MSC-derived factors act on cancer cells to release cytokines, inflammatory mediators and angiogenic factors, and simultaneously inhibit immune cell function [11]. We first analyzed the effect of conditioned media from AT-MSCs and BM-MSCs on global long interspersed element-1 (LINE-1) methylation levels in human tongue squamous carcinoma (HSC-3) cells, and the same for HSC-3-derived conditioned media on AT-MSCs and BM-MSCs (Figure 1). We examined the tumorigenic potential of AT-MSCs on OTSCC by evaluating the proliferation, migration and invasion of HSC-3 and dysplastic oral keratinocyte (DOK) cells. Mexoal.mSciin. 2e0d20,th21e, 6t4u5m5 origenic potential of AT-MSCs on OTSCC by evaluating the prolifera3toiof n15, migration and invasion of HSC-3 and dysplastic oral keratinocyte (DOK) cells

Results
Cell Cultures
MSCs Characterization
Culture of MSCs and HSC-3 Cells in Conditioned Media
Gene Expression Analysis with qRT-PCR
LINE-1 Methylation Analysis
Organotypic Myoma Discs
Immunohistochemical Staining of the Myoma Discs
Scratch-Wound Cell Migration Assay
Microscopic and Histomorphometric Analysis
Findings
4.10. Statistical Analysis
Full Text
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