Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts.

Oncotarget
Silvia CufíJavier A Menendez

Abstract

Trastuzumab-refractory breast cancer stem cells (CSCs) could also explain the high rate of primary resistance to single-agent trastuzumab in HER2 gene-amplified breast cancer patients. The identification of agents with strong selective toxicity for trastuzumab-resistant breast CSCs may have tremendous relevance for how HER2+ breast cancer patients should be treated. Using the human breast cancer cell line JIMT-1, which was established from the pleural metastasis of a patient who was clinically resistant to trastuzumab ab initio, we examined whether preferential killing of the putative CD44+CD24-/low breast CSC population might be sufficient to overcome primary resistance to trastuzumab in vivo. Because recent studies have shown that the anti-diabetic biguanide metformin can exert antitumor effects by targeted killing of CSC-like cells, we explored whether metformin's ability to preferentially kill breast cancer initiating CD44+CD24-/low cells may have the potential to sensitize JIMT-1 xenograft mouse models to trastuzumab. Upon isolation for breast cancer initiating CD44+CD24-/low cells by employing magnetic activated cell sorting, we observed the kinetics of metformin-induced killing drastically varied among CSC and non-CSC...Continue Reading

References

Mar 5, 2009·Journal of Mammary Gland Biology and Neoplasia·Philippe L BedardMartine J Piccart-Gebhart
May 18, 2010·Biochemical and Biophysical Research Communications·Cristina Oliveras-FerrarosJavier A Menendez

❮ Previous
Next ❯

Citations

Dec 20, 2012·Journal of Biomedicine & Biotechnology·Cord Naujokat, Roman Steinhart
Dec 29, 2012·Current Diabetes Reports·Etan Orgel, Steven D Mittelman
Apr 11, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Sanambar SadighiSamad Muhammadnejad
Jun 18, 2014·Nature Reviews. Endocrinology·Jiyoung ParkPhilipp E Scherer
Mar 10, 2016·Breast Cancer Research and Treatment·Indira PandiriJeong Woo Park
Apr 8, 2017·Cell Cycle·Elisabet CuyàsJavier A Menendez
Sep 23, 2018·International Journal of Molecular Sciences·Hans-Juergen Schulten
Sep 7, 2013·Oncotarget·Alexandra CanoniciAnthony Kong
Sep 26, 2015·Current Pharmacology Reports·Michael E GrossmannMargot P Cleary
Sep 13, 2014·International Journal of Oncology·Katarzyna BrodowskaDemetrios G Vavvas
May 11, 2016·Pharmaceuticals·Panagiota PapanagnouMaria Tsironi
Jan 8, 2017·Journal of Experimental & Clinical Cancer Research : CR·Zhikun MaXiaohe Yang
Jan 18, 2018·Acta Biochimica Et Biophysica Sinica·Nipun Saini, Xiaohe Yang
Sep 5, 2020·Cancers·Samson Mathews SamuelDietrich Büsselberg
Mar 5, 2013·Oncotarget·James A McCubreyZoya N Demidenko
Oct 18, 2014·Frontiers in Oncology·Javier A Menendez, Tomás Alarcón
May 9, 2013·Oncotarget·Jonathan FeldAmit K Verma
Apr 26, 2014·Immunotherapy·Cord Naujokat
Sep 21, 2012·Cell Cycle·Cristina Oliveras-FerrarosJavier A Menendez

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
xenograft

Related Concepts

Related Feeds

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.