Discovery Park Undergraduate Research Internship Program

"CPIP: Osmotin, a potential anti-inflammatory agent in breast cancer"

About the Project

Project Time & Type:
Full-Year 2010 - CPIP
Research area(s):
Breast Cancer Research
Project Description:
Breast cancer is one of the leading causes of deaths amongst women worldwide. The epidemic of obesity is associated with increased breast cancer incidence and morbidity and a heightened state of inflammation. Evidence indicates that adipocytes, through production of hormones that regulate energy homeostasis, are important regulators of growth and progression in many types of cancers. Adiponectin is one of these hormones with demonstrated anti-diabetic and anti-inflammatory effects that inhibit human breast cancer cell proliferation in vitro. Low plasma levels of adiponectin are associated with higher incidence of breast cancer in humans. Studies in mice support that adiponectin has significant anti-tumor potential. Given that low plasma adiponectin levels are also associated with obesity and the incidence of obesity-related breast cancer is rising, there is great interest in cancer-prevention and treatment modalities based on adiponectin physiology. Our group has recently shown that the tobacco plant protein osmotin is a structural homolog of adiponectin and mimics biological activities of adiponectin in mammalian skeletal muscle cells via cell-surface adiponectin receptors. Leptin is an adipose-secreted factor that acts inversely to adiponectin. Leptin has been shown to stimulate proliferation, inhibit apoptosis, promote cell invasion/metastasis, and modulate the extracellular matrix (ECM) in a number of cell types including human MCF-7 cells. Leptin levels increase in obese individuals and have been associated with a pro-inflammatory response. Tumor associated macrophages (TAM) play a role in enhancing the ability of tumor cells to metastasize by secreting various proteases to breakdown the basement membrane which allows proliferating tumor cells to escape and by secreting factors like EGF which guide tumor cells to the blood vessels where they can escape into circulation. Leptin has been shown to act as a potent chemoattractant to stimulate macrophage migration. Leptin can stimulate the release of pro-inflammatory cytokines from macrophage. Inhibition of these cytokines can affect a number of different processes including microvessel density, tumor growth and invasion, and an immune response. Our central hypothesis is that osmotin will serve as an anti-tumor therapeutic by inhibiting the leptin-induced inflammatory response associated with breast cancer. In support of this hypothesis, our preliminary data demonstrates osmotin, like adiponectin, inhibits human breast cancer proliferation in vitro and is pro-apoptotic. Adiponectin and osmotin have both been shown to signal through AMPK, and we demonstrated this in breast cancer cell lines using western blotting. Wound healing assays reveal the potential for osmotin and adiponectin to be anti-migratory factors. Collectively, our data demonstrate the potential of osmotin for mimicking adiponectin physiology in breast cancer cells. This provides a foundation for the development of osmotin as a novel therapeutic agent for cancer prevention and/or progression.
Expected Student Contributions:
The intern will be involved in daily upkeep of the cell lines. Students will learn aspects of cell culture to aid in maintenance of the cell lines and for the preparation of experiments. Students will learn how to collect samples for analysis both protein and conditioned media. Students will be asked to determine the quality of the samples collected through techniques such as the BCA assays. Students will be involved in experiments to examine the role of osmotin as an anti-inflammatory agent. This will involve the use of U937 macrophages. Students will learn techniques to examine the role this compound has on macrophage migration. Also, students will learn the technique of zymography to examine enzymes activated/deactivated by this compound.
Related Website(s):
http://www.bio.purdue.edu/people/faculty/index.php?refID=160
Desired Qualifications:
Minimum GPA 3.0; some cell culture experience; ability to handle animals (rats)
Estimated Weekly Hours:
6
Department awards independent research credits for this project?
Yes, 2 credit hours

Professor in Charge

Name:
Camarillo, Ignacio
Deptartment/College:
Biological Sciences

Student Supervisor

Name:
Therese Salameh
Title:
Graduate Student

Cooperating Faculty

Name:
Ray Bressan
Deptartment/College:
Horticulture and Landscape Architecture