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Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies
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PTHrP regulates angiogenesis and bone resorption via VEGF expression
Sachiko Isowa1, Tsuyoshi Shimo, Soichiro Ibaragi
1Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama, 700-8525, Japan.
Anticancer Research
|August 5, 2010
Summary
Parathyroid hormone-related protein (PTHrP) promotes breast cancer bone metastasis by upregulating vascular endothelial growth factor (VEGF) via protein kinase C (PKC) and ERK/p38 signaling.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Parathyroid hormone-related protein (PTHrP) is crucial in breast cancer (BC) osteolytic bone metastasis.
- Its precise targets and mechanisms, particularly regarding VEGF, remain unclear.
Purpose of the Study:
- To investigate how PTHrP (1-34) signaling influences vascular endothelial growth factor (VEGF) expression in BC cells.
- To elucidate the signaling pathways involved in PTHrP-mediated VEGF regulation.
Main Methods:
- Utilized a mouse model of bone metastasis by injecting human BC cells (MDA-MB-231) intravenously.
- Assessed VEGF expression using Western blot, RT-PCR, and confocal microscopy.
- Investigated the role of protein kinase C (PKC) and downstream signaling pathways (ERK1/2, p38).
Main Results:
- PTHrP up-regulated VEGF expression in MDA-MB-231 cells.
- PTHrP-conditioned medium promoted angiogenesis and osteoclastogenesis, effects blocked by anti-VEGF treatment.
- PKC inhibition prevented PTHrP-induced ERK1/2, p38 activation, and subsequent VEGF upregulation.
Conclusions:
- PTHrP significantly modulates VEGF's pro-angiogenic and osteolytic activities in breast cancer bone metastasis.
- This modulation occurs via a PKC-dependent signaling pathway involving ERK1/2 and p38 activation.
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