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Cancer Res Treat. 2017 Oct;49(4):869-879. doi: 10.4143/crt.2016.378. Epub 2016 Dec 6.

Laminin Modulates the Stem Cell Population in LM05-E Murine Breast Cancer Cells through the Activation of the MAPK/ERK Pathway.

Author information

1
Research Area, Instituto de Oncología "Angel H. Roffo", Ciudad de Buenos Aires, Argentina.
2
Members of the Research Career, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad de Buenos Aires, Argentina.
3
Instituto de Nanosistemas, Universidad Nacional de San Martín, Campus Miguelete, San Martín, Argentina.

Abstract

PURPOSE:

We investigated the effects of laminin on the fraction of cells with self-renewing capacity in the estrogen-dependent, tamoxifen-sensitive LM05-E breast cancer cell line. We also determined whether laminin affected the response to tamoxifen.

MATERIALS AND METHODS:

The LM05-E breast cancer cell line was used as a model for all experiments. Aldehyde dehydrogenase (ALDH) activity, clonogenic and mammosphere assays were performed to measure the effects of laminin on modulation of the stem cell subpopulation. Pluripotent gene expression was analyzed by reverse transcriptase-polymerase chain reaction. The involvement of the mitogen-activated protein kinase (MAPK)/ERK pathway was determined using specific inhibitors. The effects of laminin on the response to tamoxifenwere determined and the involvement of α6 integrin was investigated.

RESULTS:

We found that pretreatment with laminin leads to a decrease in cells with the ability to form mammospheres that was accompanied by a decrease in ALDH activity. Moreover, exposure of mammospheres to laminin reduced the capacity to form secondary mammospheres and decreased the expression of Sox-2, Nanog, and Oct-4. We previously reported that 4-OH-tamoxifen leads to an increase in the expression of these genes in LM05-E cells. Treatment with signaling pathway inhibitors revealed that the MAPK/ERK pathway mediates the effects of laminin. Finally, laminin induced tamoxifen resistance in LM05-E cells through α6 integrin.

CONCLUSION:

Our results suggest that the final number of cells with self-renewing capacity in estrogen-dependent breast tumors may result from the combined effects of endocrine treatment and microenvironmental cues.

KEYWORDS:

Breast neoplasms; Estrogen receptor alpha; Laminin; MAP kinase signaling system; Stem cells

PMID:
28052658
PMCID:
PMC5654159
DOI:
10.4143/crt.2016.378
[Indexed for MEDLINE]
Free PMC Article

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