Organ specific metastasisBreast cancer lymph nodes, bon.pptVIP

* Organ specific metastasis Breast cancer: lymph nodes, bone, liver, brain and lung Prostate cancer: lymph nodes and bone Colorectal cancer: liver Melanoma: same as breast cancer + skin Stephen Paget (1889): seed and soil James Ewing (1920): hemodynamics - “plumbing” Possible Determinants of Site-Specific Metastasis Hemodynamics (“Plumbing”) 1. Blood flow patterns (How many cells are delivered to an organ?) 2. Mechanics of cell arrest, growth and extravasation “Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium.” (Glinsky and Quinn. Cancer Research. 63. July 2003). Homing 1. Chemokines “Involvement of chemokine receptors in breast cancer metastasis.” (Mueller and Zlotnick. Nature. 410. March 2001). “Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells.” (Murakami and Hwang. Cancer Research. 62. December 2002). “Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer.” (Scotton and Balkwill. Cancer Research 62. October 2002). 2. Selectins 3. Vasculature specificity Seed and Soil 1. Bone growth factors “Metastasis to bone: causes, consequences and therapeutic opportunities.” (Mundy. Nature Reviews Cancer. 2. August 2002). Possible Determinants of Site-Specific Metastasis From MacDonald and Chambers. BioEssays. 24.10. 2002. Hemodynamics vs. Seed Soil: Support for Both Hypotheses Leonard Weiss (1986): autopsy studies Breast and prostate cancer: a greater # of bone mets. than would be expected based solely on blood flow patterns. Osteosarcoma, stomach and testicular cancer: a smaller # of skin mets. than would be expected based on blood flow. - 16 primary tumor types and 8 target organs were analyzed: 66% of tumor-type-organ met. pairs explained on basis of blood flow 14%