Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Head and Neck Cancer Xenografts

Aesthet Surg J. 2016 Jan;36(1):93-104. doi: 10.1093/asj/sjv090. Epub 2015 Jun 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism*
  • Animals
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary*
  • Carcinoma, Squamous Cell
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Heterografts / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • Stem Cells / metabolism*
  • Stromal Cells / metabolism*
  • Transplantation, Heterologous