Human bone marrow mesenchymal stem cells induce collagen production and tongue cancer invasion.

Abstract

Tumor microenvironment (TME) is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs), and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC) cells by analyzing the invasion progression and gene expression pattern. In a 3-dimensional myoma organotypic invasion model the presence of BMMSCs inhibited the proliferation but increased the invasion of OTSCC cells. Furthermore, the signals originating from OTSCC cells up-regulated the expression of inflammatory chemokines by BMMSCs, whereas BMMSC products induced the expression of known invasion linked molecules by carcinoma cells. Particularly, after the cell-cell interactions, the chemokine CCL5 was abundantly secreted from BMMSCs and a function blocking antibody against CCL5 inhibited BMMSC enhanced cancer invasion area. However, CCL5 blocking antibody did not inhibit the depth of invasion. Additionally, after exposure to BMMSCs, the expression of type I collagen mRNA in OTSCC cells was markedly up-regulated. Interestingly, also high expression of type I collagen N-terminal propeptide (PINP) in vivo correlated with the cancer-specific mortality of OTSCC patients, whereas there was no association between cancer tissue CCL5 levels and the clinical parameters. In conclusion, our results suggest that the interaction between BMMSC and carcinoma cells induce cytokine and matrix molecule expression, of which high level of type I collagen production correlates with the prognosis of OTSCC patients.

• Authors: Sirpa Salo, Carolina Bitu, Kalle Merkku, Pia Nyberg, Ibrahim O Bello, Jussi Vuoristo, Meeri Sutinen, Hannu Vähänikkilä, Daniela E Costea, Joonas H Kauppila, Joonas Kauppila, Petri Lehenkari, Dan Dayan, Marilena Vered, Juha Risteli, Tuula Salo
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e77692 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24204919 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL5 protein, human
• Chemokine CCL5
• Collagen

Topics

• Aged
• Bone Marrow Cells (metabolism, pathology)
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Communication (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Chemokine CCL5 (genetics, metabolism)
• Collagen (metabolism)
• Female
• Fibroblasts (metabolism, pathology)
• Gene Expression (genetics)
• Humans
• Male
• Mesenchymal Stem Cells (metabolism, pathology)
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology)
• Tongue Neoplasms (genetics, metabolism, pathology)
• Tumor Microenvironment (genetics)
• Up-Regulation (genetics)