Adipose stem cell crosstalk with chemo-residual breast cancer cells: implications for tumor recurrence.

Published

Journal Article

PURPOSE: Most triple-negative breast cancer (TNBC) patients exhibit an incomplete response to neoadjuvant chemotherapy, resulting in chemo-residual tumor cells that drive tumor recurrence and patient mortality. Accordingly, strategies for eliminating chemo-residual tumor cells are urgently needed. Although stromal cells contribute to tumor cell invasion, to date, their ability to influence chemo-residual tumor cell behavior has not been examined. Our study is the first to investigate cross-talk between adipose-derived stem cells (ASCs) and chemo-residual TNBC cells. We examine if ASCs promote chemo-residual tumor cell proliferation, having implications for tumor recurrence. METHODS: ASC migration toward chemo-residual TNBC cells was tested in a transwell migration assay. Importance of the SDF-1α/CXCR4 axis was determined using neutralizing antibodies and a small molecule inhibitor. The ability of ASCs to drive tumor cell proliferation was analyzed by culturing tumor cells ± ASC conditioned media (CM) and determining cell counts. Downstream signaling pathways activated in chemo-residual tumor cells following their exposure to ASC CM were studied by immunoblotting. Importance of FGF2 in promoting proliferation was assessed using an FGF2-neutralizing antibody. RESULTS: ASCs migrated toward chemo-residual TNBC cells in a CXCR4/SDF-1α-dependent manner. Moreover, ASC CM increased chemo-residual tumor cell proliferation and activity of extracellular signal-regulated kinase (ERK). An FGF2-neutralizing antibody inhibited ASC-induced chemo-residual tumor cell proliferation. CONCLUSIONS: ASCs migrate toward chemo-residual TNBC cells via SDF-1α/CXCR4 signaling, and drive chemo-residual tumor cell proliferation in a paracrine manner by secreting FGF2 and activating ERK. This paracrine signaling can potentially be targeted to prevent tumor recurrence.

Full Text

Duke Authors

Cited Authors

  • Lyes, MA; Payne, S; Ferrell, P; Pizzo, SV; Hollenbeck, ST; Bachelder, RE

Published Date

  • April 2019

Published In

Volume / Issue

  • 174 / 2

Start / End Page

  • 413 - 422

PubMed ID

  • 30594967

Pubmed Central ID

  • 30594967

Electronic International Standard Serial Number (EISSN)

  • 1573-7217

Digital Object Identifier (DOI)

  • 10.1007/s10549-018-05103-w

Language

  • eng

Conference Location

  • Netherlands