Distinct effects of adipose-derived stem cells and adipocytes on normal and cancer cell hierarchy

Manjushree Anjanappa, Riesa Burnett, Michael A. Zieger, Stephanie Merfeld-Clauss, William Wooden, Keith March, Sunil Tholpady, Harikrishna Nakshatri

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Adipose-derived stem cells (ASC) have received considerable attention in oncology because of the known direct link between obesity and cancer as well as the use of ASCs in reconstructive surgery after tumor ablation. Previous studies have documented how cancer cells commandeer ASCs to support their survival by altering extracellular matrix composition and stiffness, migration, and metastasis. This study focused on delineating the effects of ASCs and adipocytes on the self-renewal of stem/progenitor cells and hierarchy of breast epithelial cells. The immortalized breast epithelial cell line MCF10A, ductal carcinoma in situ (DCIS) cell lines MCF10DCIS.com and SUM225, and MCF10A-overexpressing SRC oncogene were examined using a mammosphere assay and flow cytometry for the effects of ASCs on their self-renewal and stem-luminal progenitor-differentiated cell surface marker profiles. Interestingly, ASCs promoted the self-renewal of all cell types except SUM225. ASC coculture or treatment with ASC conditioned media altered the number of CD49fhigh/EpCAMlow basal/stem-like and CD49fmedium/EpCAMmedium luminal progenitor cells. Among multiple factors secreted by ASCs, IFNg and hepatocyte growth factor (HGF) displayed unique actions on epithelial cell hierarchy. IFNg increased stem/progenitor-like cells while simultaneously reducing the size of mammospheres, whereas HGF increased the size of mammospheres with an accompanying increase in luminal progenitor cells. ASCs expressed higher levels of HGF, whereas adipocytes expressed higher levels of IFNg. As luminal progenitor cells are believed to be prone for transformation, IFNg and HGF expression status of ASCs may influence susceptibility for developing breast cancer as well as on outcomes of autologous fat transplantation on residual/dormant tumor cells. Implications: This study suggests that the ratio of ASCs to adipocytes influences cancer cell hierarchy, which may impact incidence and progression.

Original languageEnglish (US)
Pages (from-to)660-671
Number of pages12
JournalMolecular Cancer Research
Volume14
Issue number7
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Anjanappa, M., Burnett, R., Zieger, M. A., Merfeld-Clauss, S., Wooden, W., March, K., Tholpady, S., & Nakshatri, H. (2016). Distinct effects of adipose-derived stem cells and adipocytes on normal and cancer cell hierarchy. Molecular Cancer Research, 14(7), 660-671. https://doi.org/10.1158/1541-7786.MCR-16-0055