When healthy cells stimulate the migration of tumor cells

June 15, 2017
Left: Cells carrying the traditional GPER (fluorescent cytoplasm). Right: Cells carrying the nuclear variant of GPER (fluorescent nucleus). Credit: Université de Genève

Estrogens act as a driving force of both healthy and cancerous mammary cell growth by binding to receptors that include a type named GPER, which is generally located in cell membranes. Recent studies have, however, revealed the unusual presence of this receptor in the nuclei of fibroblasts - cells of the connective tissue - surrounding mammary tumor cells. Researchers at the University of Geneva (UNIGE), Switzerland, have discovered that this is in fact another version of GPER, a nuclear variant of this receptor, with different properties. The fibroblasts carrying this variant promote the migration of neighboring malignant cells, thus participating in the process of tumor metastasis. This research, which may pave the way to a novel therapeutic strategy, is published in the journal Oncotarget.

Estrogens play a crucial role in the genesis of the majority of breast cancers, promoting the survival, proliferation and invasiveness of tumor . These hormones act by binding to their receptors, which fall into two groups, ER and GPER, whose properties differ.

The team of Didier Picard, professor at the Department of Cell Biology of the Faculty of Sciences of UNIGE, is interested in GPER receptors, whose effects on breast cancer are less well known than those of the ER family. "By analyzing a breast tumor biopsy, our colleagues at the University of Calabria, who participated in this study, discovered GPER receptors in the nucleus of fibroblasts present around the malignant cells, whereas they had always been localized elsewhere before", says the biologist.

Fibroblasts abound around the tumor

Fibroblasts, constituents of the , are part of the microenvironment of the tumors. "Knowing that cancer cells interact with neighboring healthy cells to survive and grow, we wanted to find out whether the GPER receptors observed in the nucleus of these fibroblasts were involved in this process", explains Marco Pupo, first author of the study.

The researchers have discovered the existence of another version of GPER: "This genetic variant results from a tiny change, a single nucleotide, in the gene that codes for the GPER receptor. This is sufficient to induce its relocation to the nucleus. We detected the presence of this same version of the gene in the fibroblasts of the eight other biopsies we analyzed, from the University Hospital of Geneva", states Didier Picard.

The genetic variant of GPER could predispose to breast cancer

The nuclear variant also acquires new properties. Indeed, unlike the GPER receptor hitherto described, it is capable of stimulating the expression of genes involved in malignant growth. Moreover, present in the microenvironment and carrying nuclear GPER secrete molecules that promote the migration of neighboring .

"We have deciphered an important element of the dialogue between the and the adjacent healthy cells, and we want to find out the nature of the fibroblastic factors involved in the process of ", specifies Marco Pupo. It may be worth thinking about specifically interfering with the nuclear functions of GPER as a novel therapeutic strategy.

Explore further: Understanding the resistance to treatments against breast cancer

More information: Marco Pupo et al. A genetic polymorphism repurposes the G-protein coupled and membrane-associated estrogen receptor GPER to a transcription factor-like molecule promoting paracrine signaling between stroma and breast carcinoma cells, Oncotarget (2017). DOI: 10.18632/oncotarget.18156

Related Stories

Understanding the resistance to treatments against breast cancer

June 20, 2016
Estrogens are responsible for the survival and proliferation of tumor cells in 70% of all breast cancer cases. The most frequently used treatment to fight this variety of tumors relies on anti-estrogens such as tamoxifen. ...

Gene variant identified as a heart disease risk factor for women

July 22, 2014
When it comes to heart disease, Dr. Ross Feldman says women are often in the dark. Historically, it was thought that heart disease was a men's-only disease, however, data has shown that post-menopausal women are just as likely ...

Researchers identify estrogen's role in regulating common health disease risks

November 13, 2014
What makes some women more susceptible to heart disease than others? To help answer that question, researchers at Western University's Robarts Research Institute have identified that an estrogen receptor, previously shown ...

Researchers describe how tumors recruit and use stem cells to support tumor growth and progression

October 20, 2016
A new study has identified a mechanism used by tumors to recruit stem cells from bone and convert them into cancer-associated fibroblasts (CAFs) that facilitate tumor progression. This work, which pinpoints the specific biochemical ...

Researchers discover tumor cells stiffen before becoming invasive

May 16, 2017
A study recently published in Nature Communications shows that breast cancer cells undergo a stiffening state prior to becoming malignant. The discovery, made by a research team led by Florence Janody, from Instituto Gulbenkian ...

Study reveals how normal cells fuel tumor growth

December 21, 2011
A new study published in the journal Nature Cell Biology has discovered how normal cells in tumors can fuel tumor growth.

Recommended for you

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

One to 10 mutations are needed to drive cancer, scientists find

October 19, 2017
For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger ...

Suicide molecules kill any cancer cell

October 19, 2017
Small RNA molecules originally developed as a tool to study gene function trigger a mechanism hidden in every cell that forces the cell to commit suicide, reports a new Northwestern Medicine study, the first to identify molecules ...

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

Fundamental research enhances understanding of major cancer gene

October 19, 2017
New research represents a promising step towards better understanding of a key cancer gene. A long-running collaboration between researchers at the Babraham Institute, Cambridge and the AstraZeneca IMED Biotech Unit reveals ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.