Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity.
Duong MN., Cleret A., Matera EL., Chettab K., Mathé D., Valsesia-Wittmann S.
Animal Study, published in Breast Cancer Res (2015) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Breast Cancer Res (2015)
- Country
- England
- Reported sample size
- —
- Source database
- PubMed
- PMID
- 25908175
- PMCID
- PMC4482271
- DOI
- 10.1186/s13058-015-0569-0
- Citations
- 91
Abstract (original English)
Introduction Trastuzumab has been used in the treatment of human epidermal growth factor receptor 2 (HER2)-expressing breast cancer, but its efficacy is limited by de novo or acquired resistance. Although many mechanisms have been proposed to explain resistance to trastuzumab, little is known concerning the role of the tumor microenvironment. Given the importance of antibody-dependent cellular cytotoxicity (ADCC) in the antitumor effect of trastuzumab and the abundance of adipose tissue in the breast, we investigated the impact of adipocytes on ADCC. Methods We set up a coculture system to study the effect of adipocytes on ADCC in vitro. The results were validated in vivo in a mouse xenograft model. Results We found that adipocytes, as well as preadipocytes, inhibited trastuzumab-mediated ADCC in HER2-expressing breast cancer cells via the secretion of soluble factors. The inhibition of ADCC was not due to titration or degradation of the antibody. We found that adipose cells decreased the secretion of interferon-γ by natural killer cells, but did not alter natural killer cells' cytotoxicity. Preincubation of breast cancer cells with the conditioned medium derived from adipocytes reduced the sensitivity of cancer cells to ADCC. Using a transcriptomic approach, we found that cancer cells undergo major modifications when exposed to adipocyte-conditioned medium. Importantly, breast
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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