Osteoblast-Derived PTHRP and Breast Cancer Bone Metastasis
Final rept. 2 Sep 2003-1 Sep 2004
MCGILL UNIV MONTREAL (CANADA)
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Metastases to bone, lung, and other organs are common and catastrophic consequences of breast cancer progression. There is therefore an urgent need to improve current therapies that address cancer growth and spread. Parathyroid hormone-related protein PTHrP, also referred to as parathyroid hormone-like protein PTHLP is a secreted factor expressed in almost all normal fetal and adult tissues, acting as an autocrine, paracrine, or intracrine factor in a wide range of developmental and physiological processes. Although PTHrPs dysregulated expression has traditionally been associated with oncogenic pathologies as the major causative agent of malignancy-associated hypercalcemia, recent evidence revealed a driving role in skeletal metastasis progression. Here, we demonstrate that PTHrP is also closely involved in breast cancer initiation, growth and metastasis to bone and lung through mechanisms separate from its bone turnover action, and we suggest that PTHrP as facilitator of oncogenes could serve as a novel target for therapeutic intervention.
- Medicine and Medical Research