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Download BCC_Activity_PPT Slide Set_Teacher_July 2014
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Companion PowerPoint slide set Obesity-associated breast cancer risk: a role for epigenetics? This teacher slide set was created by Dana Haine, MS, of the UNC Center for Environmental Health and Susceptibility, which is funded by the National Institute of Environmental Health Sciences (P30-ES010126). Dr. Liza Makowski Studies Basal-like Breast Cancer (BBC) • Aggressive cancer • No specific drug therapies • Short survival time if it spreads beyond breast tissue (metastasis) • More prevalent in young pre-menopausal women • More prevalent in African Americans • Obesity is a risk factor for all breast cancers Number of weeks until tumor formation Obesity causes BBC tumors to form at a faster rate compared to lean mice Fat-fed (Lean) Fat-fed (obese) Cross-section of mammary (milk) duct http://www.womenshealth.gov/breast-cancer/what-is-breast-cancer/ Label epithelial cells, fat cells and fibroblasts on the diagram below: Inside (lumen) of milk duct Adipocytes (Fat cells) Fibroblasts Stroma of mammary tissue Epithelial Cells of Milk Duct Inside (lumen) of milk duct Immune cells are also present but are not shown in order to simplify schematic of the stroma. microenvironment Cancer & the microenvironment HEALTHY CELL CANCER CELL The microenvironment (“soil”) surrounding a cell (“seed”) plays a role in tumor formation. Liza Makowski: “How does obesity alter the microenvironment in breast cancer?” Cell to cell communication HGF-cMET paracrine signaling HGF C-met receptor Adapted from Melissa Troester/Patricia Casbas-Hernandez @ UNC Cell to cell communication HGF-cMET paracrine signaling HGF cMET receptor HGF P C-met Prevents cell death Promotes Cell Division Promotes motility (leads to Metastasis) Melissa Troester/Patricia Casbas-Hernandez @ UNC Promotes growth of blood vessels to supply tumor OD x % HGF+ staining in Normal Mammary Obesity increases levels of HGF mRNA and protein in normal mammary tissue 2.0 1.5 * 1.0 0.5 0.0 10% 45% Diets 60% Sundaram, S., Makowski, L., et. al. Cancer Prevention Research (Under Review, 2012) Ex vivo cell culture model Lean Mice Isolate Fibroblasts Culture Fibroblasts Measure HGF Secretion Normal Cell Division HGF Secretion Cancerassociated Obese Mice HGF Secretion HGF Secretion HGF secretion in cultured cells Lean Mice Isolate Fibroblasts Normal Cancerassociated Obese Mice Culture Fibroblasts HGF Secretion Phospho-c-Met c-Met Control BBC Tumor cell line + mHGF C. BBC Tumor cell line + CM BBC Tumor cell line Analysis of c-Met protein levels in BBC tumor cell line “How does obesity alter the microenvironment in breast cancer?” Signal Fat cell Fibroblast c-Met activation HGF Secretion Epithelial cell Microenvironment Conclusion: growth factor signaling pathway (HGF/cMet) was upregulated with obesity. Cancer formation
