Oncotarget: Induction of phenotypic changes in HER2-postive breast cancer cells

October 17, 2020

The cover for issue 30 of Oncotarget features Figure 4, "RNAseq results demonstrating differences between normal, cancer, and redirected cells," by Frank-Kamenetskii, et al. which reported that the influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not.

Here using in vivo and in vitro models the Oncotarget authors demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells.

Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells.

The authors have termed this phenomenon “cancer cell redirection.” Once breast cancer cells are redirected, either in vivo or in vitro, they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile.

These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.

Dr. Brian W. Booth from Clemson University said, "Tissue microenvironments are complex regions that consist of multiple cell types such as epithelial cells, adipocytes, fibroblasts, vascular endothelial cells, resident and transient immune cells, and somatic stem cells"

"Tissue microenvironments are complex regions that consist of multiple cell types such as epithelial cells, adipocytes, fibroblasts, vascular endothelial cells, resident and transient immune cells, and somatic stem cells"


Tissue microenvironments are complex regions that consist of multiple cell types such as epithelial cells, adipocytes, fibroblasts, vascular endothelial cells, resident and transient immune cells, and somatic stem cells.

Using rodent models, it was discovered that when mammary epithelial cells were transplanted into a mammary fat pads of pre-pubescent female mice devoid of endogenous epithelium an entire functional mammary outgrowth could be recapitulated regardless of age or parity status of the transplanted cells.

When dispersed cell suspensions of mammary epithelial cells are used in these models the cells participate in the formation of new microenvironments allowing for the normal development of mammary outgrowths.

Stem cells isolated from the central nervous system, bone marrow, testes, and embryonic stem cells have been introduced into reforming mammary microenvironments and adopted mammary epithelial phenotypes.

Lineage-traced daughter cells of the non-mammary stem cells participated in the normal development of mammary ductal trees and differentiated into luminal epithelial cells, myoepithelial cells, and milk protein-producing secretory epithelial cells during lactation.

The Booth Research Team concluded in their OncotargetResearch Paper, "our data collectively argue that epithelial cells provide signals that influence HER2+ breast cancer cells to reduce tumor formation. The reduction in tumor-forming capacity is due to a shift in gene expression profiles from a tumorigenic towards a normal epithelial profile. The phenotypic switch, known as cancer cell redirection, includes changes in the activity of multiple intracellular signaling pathways. Modulation of these affected pathways may be a new approach towards cancer treatments."

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27679

Full text - https://www.oncotarget.com/article/27679/text/

Correspondence to - Brian W. Booth - brbooth@clemson.edu

Keywords - breast cancer, cancer cell redirection, microenvironment, stem cells

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud -https://soundcloud.com/oncotarget
Facebook -https://www.facebook.com/Oncotarget/
Twitter -https://twitter.com/oncotarget
LinkedIn -https://www.linkedin.com/company/oncotarget
Pinterest -https://www.pinterest.com/oncotarget/
Reddit -https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Impact Journals LLC

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.