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Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Head and Neck Cancer
Brian G Rowan1, Eduardo A Lacayo1, Mei Sheng1
1Dr Rowan is Piltz Professor of Cancer Research, Tulane Cancer Center, and Associate Professor and Interim Chair, Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana. Drs Lacayo and Sheng are Postdoctoral Researchers, Dr Anbalagan is an Instructor, and Mr Jones is a Technician, Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana. Dr Gimble is Adjunct Professor, Departments of Medicine, Surgery, and Structural and Cellular Biology, and the Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana. Mr Joseph is a Medical Student and Dr Chiu is an Associate Professor, Department of Plastic Surgery, New York University Langone Medical Center, New York, New York. Dr Friedlander is the Chairman, Department of Otolaryngology, Tulane University School of Medicine, New Orleans, Louisiana.
Background:
Fat grafting has become popular for repair of postsurgical/postradiation defects after head/neck cancers resection. Fat graft supplementation with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve graft viability/efficacy, although the impact of ASCs on head/neck cancer cells is unknown.
Objectives:
To determine whether ASCs affect growth, migration, and metastasis of human head/neck cancer.
Methods:
Human Cal-27 and SCC-4 head/neck cancer cells were co-cultured human ASCs, or treated with ASC conditioned medium (CM), and cancer cell growth/migration was assessed by MTT, cell count, and scratch/wound healing assays in vitro. Co-injection of 3 × 10(6) Cal-27/green fluorescent protein (GFP) cells and ASCs into the flank of NUDE mice assessed ASC effect on tumor growth/morphology. Quantitation of human chromosome 17 DNA in mouse organs assessed ASC effects on micrometastasis. Primary tumors were evaluated for markers of epithelial-to-mesenchymal transition, matrix metalloproteinases, and angiogenesis by immunohistochemistry.
Results:
Co-culture of Cal-27 or SCC-4 cells with ASCs from 2 different donors or ASC CM had no effect on cell growth in vitro. However, ASC CM stimulated Cal-27 and SCC-4 migration. Co-injection of ASCs from 2 different donors with Cal-27 cells did not affect tumor volume at 6 weeks, but increased Cal-27 micrometastasis to the brain. Evaluation of tumors sections from 1 ASC donor co-injection revealed that ASCs were viable and well integrated with Cal-27/GFP cells. These tumors exhibited increased MMP2, MMP9, IL-8, and microvessel density.
Conclusions:
Human ASCs did not alter growth of human head/neck cancer cells or tumor xenografts, but stimulated migration and early micrometastasis to mouse brain.
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