stopping breast cancer spread (not her2 specific so far)

[Lani]

will try to read original article, when have time later today

Stopping breast cancer spread
[Eureka News Service]

Most people who die from breast cancer do not die as a result of their breast tumor but because their cancer has spread (metastasized) to other parts of their body, often their lungs or bones. A team of researchers led by Richard Kremer, at McGill University Health Centre, Montréal, has used a mouse model of human breast cancer to identify a potential new target for slowing breast tumor progression and metastasis.

The protein PTHrP is frequently found to be expressed in breast tumors, but whether it plays a role in disease progression has not been determined. Kremer and colleagues found that in one mouse model of breast cancer PTHrP promoted primary tumor initiation, tumor progression, and metastasis to other parts of the body. As neutralizing the effects of PTHrP with therapeutics known as antibodies slowed the progression and metastasis of human breast cancer cells transplanted into mice, Kremer and colleagues suggest this approach should be considered as a potential new strategy for treating people with breast cancer.

OPEN ACCESS: PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target
[Journal of Clinical Investigation]

Parathyroid hormone-related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and sugg