title: 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.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Salo
authors.forename: Carolina
authors.initials: C
authors.lastname: Bitu
authors.forename: Kalle
authors.initials: K
authors.lastname: Merkku
authors.forename: Pia
authors.initials: P
authors.lastname: Nyberg
authors.forename: Ibrahim O
authors.initials: IO
authors.lastname: Bello
authors.forename: Jussi
authors.initials: J
authors.lastname: Vuoristo
authors.forename: Meeri
authors.initials: M
authors.lastname: Sutinen
authors.forename: Hannu
authors.initials: H
authors.lastname: Vähänikkilä
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Costea
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.forename: Joonas
authors.initials: J
authors.lastname: Kauppila
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
authors.forename: Dan
authors.initials: D
authors.lastname: Dayan
authors.forename: Marilena
authors.initials: M
authors.lastname: Vered
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D003094:Collagen