New mouse model unlocks drug testing of hormone-sensitive human breast
cancer
Mice engineered to produce human prolactin support growth and distant
spread of estrogen receptor-positive breast tumors from patients

Date:
October 4, 2021
Source:
Medical College of Wisconsin
Summary:
Scientists have created mice with a hormone profile that
causes growth and metastatic spread of implanted human breast
tumors. Results show that the team created a new mouse breed, called
NSG-Pro, that produces levels of human prolactin similar to those in
patients with metastatic estrogen receptor-positive breast cancer.



FULL STORY ========================================================================== Scientists at the Medical College of Wisconsin Cancer Center and an international team of collaborators have generated mice with an improved hormone profile that supports growth and metastatic spread of implanted
human breast tumors.


==========================================================================
The majority of breast cancer deaths are caused by estrogen receptor(ER)- positive tumors. It has been a long-standing challenge to grow untreated
ER- positive breast tumors from patients in mice. The shortage of such
human breast tumor models has hampered efforts to identify better drugs
or drug combinations. More effective treatments are needed to prevent
the frequent development of resistance to current therapies and thereby
reduce mortality from breast cancer.

ER-positive breast tumors are sensitive to the hormone prolactin,
most known for promoting milk-production in mothers. The investigators
had previously discovered that mouse prolactin fails to activate human prolactin receptors and speculated that this hormonal shortcoming was
key to the poor growth of human ER-positive breast cancer in mice.

This new study reports that by modifying the mouse prolactin gene,
the team generated a mouse breed that produces blood levels of human
prolactin similar to the levels detected in patients. This new mouse
model, called NSG-Pro, supports greatly enhanced growth of implanted ER-positive human breast cancers.

Molecular pathway analyses of the tumors revealed that prolactin
collaborates with estrogen and Her2, two well-established growth factors
for breast cancer.

The team has now generated a panel of transplantable estrogen-dependent patient-derived breast tumor models in NSG-Pro mice. Several of the new
tumor lines recapitulate disease progression in patients by spreading
to distant organs when implanted into the mammary glands of NSG-Pro
mice. The research appears in the September 15 online issue of the
journal Science Advances.

"We are particularly excited about the opportunity to study distant
metastases and test the effectiveness of drugs on advanced stage
ER-positive breast cancer, because until now such experimental models
have not been available," says Hallgeir Rui, WBCS Endowed Professor of
Breast Cancer Research; director of the MCW Tissue Bank; and professor
and vice chair of Research, Pathology at MCW. "This is particularly
important because breast cancer patients die from distant metastases." Intriguingly, after surgically removing the primary tumors from the mouse mammary glands, the team documented that two different prolactin-blocking treatments inhibited the growth of cancer cells that had spread to
the lungs.

While further studies are needed, the results raise the prospect that prolactin-targeted drugs may benefit some patients with metastatic
ER-positive breast cancer.

"The NSG-Pro mouse model provides previously inaccessible precision
medicine approaches for ER-positive human breast cancers," said Yunguang
Sun, MD, PhD, joint lead author of the study and assistant professor in Pathology & Laboratory Medicine at MCW.

========================================================================== Story Source: Materials provided by Medical_College_of_Wisconsin. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Yunguang Sun, Ning Yang, Fransiscus E. Utama, Sameer S. Udhane,
Junling
Zhang, Amy R. Peck, Alicia Yanac, Katherine Duffey, John
F. Langenheim, Vindhya Udhane, Guanjun Xia, Jess F. Peterson,
Julie M. Jorns, Marja T.

Nevalainen, Romain Rouet, Peter Schofield, Daniel Christ,
Christopher J.

Ormandy, Anne L. Rosenberg, Inna Chervoneva, Shirng-Wern Tsaih,
Michael J. Flister, Serge Y. Fuchs, Kay-Uwe Wagner, Hallgeir
Rui. NSG-Pro mouse model for uncovering resistance mechanisms and
unique vulnerabilities in human luminal breast cancers. Science
Advances, 2021; 7 (38) DOI: 10.1126/sciadv.abc8145 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211004115139.htm

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