Breast Cancer Metastasis to Bone



Breast Cancer Metastasis to Bone

Project Description

Over a million women worldwide are diagnosed annually with breast cancer. Breast cancer metastasizes to bone in the majority of patients with advanced disease, and results in severe bone pain due to uncontrolled bone resorption. My summer research project will help 1) characterize the effects of metastatic breast cancer on bone and 2) assess if increased bone turnover due to inadequate calcium intake increases breast cancer metastasis to bone in a mouse model.

Bone turnover (bone resorption followed by formation) is normal and essential for mobilizing calcium from bone into blood and for repair of everyday wear fatigue damage in bone. It is currently believed that circulating breast tumor cells lodge in bone marrow and initiate increased bone resorption which causes the release of growth factors from bone that, in turn, stimulate tumor growth. We hypothesize that high rates of bone turnover prior to metastasis increase breast cancer metastasis to bone. Calcium absorption decreases with age resulting in an increased risk for calcium insufficiency. Therefore, we will investigate whether increased bone turnover, due to inadequate dietary calcium, is an independent risk factor for breast cancer metastasis to bone and accelerates tumor growth once cancer is established within the bone microenvironment.

Understanding the mechanism of breast cancer metastasis to bone is important towards preventing and/or developing treatment therapies for the disease. Unfortunately, the study of breast cancer metastasis has been hindered by lack of appropriate animal models. Historically, it has been very difficult to study breast cancer metastasis because most tumors in animal models do not metastasize to bone. An animal model (mouse) is now available where mouse breast tumor cells (called 4T1 cells) injected into mouse mammary glands metastasize to bone and other tissues. The Skeletal Biology Laboratory is performing studies using this model to determine the effect of elevated bone turnover, due to low calcium intake, on spontaneous metastasis of 4T1 cells from mammary pad to bone. The animal part of this experiment has been completed. Mice were divided into 2 groups (normal calcium and low calcium) and 4T1 cells injected into the mammary pad. The mice were sacrificed after 2 weeks (determined previously as optimal time) and bones removed for analysis. I will be responsible for analysis of bone architecture using micro-computed tomography (microCT).

If our hypothesis is correct and mice on the low calcium diet exhibit increased metastasis and/or tumor growth, lowering bone turnover through a dietary calcium approach should reduce the risk of tumor metastasis to bone. If correct, this can be easily translated to clinical practice; increasing the amount of calcium by eating calcium rich foods or taking supplements may reduce the likelihood of metastasis to bone in breast cancer survivors. As someone who has personally seen the effects of cancer, I understand the significance of cancer research. When I was a young boy, my grandmother passed away from cancer. She first was diagnosed with lung cancer, which later metastasized to other tissues. I know the pain she felt from the cancer was very intense, and her passing was a small comfort to know she would no longer suffer. In addition, my own mother is a two time cancer survivor. Seeing my mother suffer through these experiences, allowed me to witness firsthand the devastation cancer causes. This has definitely played an integral part in my interest to be a part of this cancer research project; it is my desire to use my knowledge and skills to aid cancer research, so we can find solutions to this horrible disease. My interest in gerontology also stems from my personal experiences with cancer, because I greatly hope to improve the lives of cancer survivors in their later years. I believe my passion for cancer research would make me a great candidate for an apprenticeship in the Skeletal Biology Laboratory this summer.

Synergy

Breast cancer metastasis to bone occurs in approximately 80% of patients with late stage disease. This results in a severe reduction in the quality of life for patients, who suffer chronic pain. It may also act as a stepping stone for further metastasis. By better understanding the mechanisms of breast cancer metastasis to bone and other tissues and subsequent tumor growth, we become better positioned to prevent/treat the occurrence. Therefore, I look at successful completion of this research project as a beginning. Dr. Iwaniec, the lead researcher in this project is an expert in bone physiology, and in recent years has applied her knowledge to understanding how breast cancer cells metastasize to the skeleton and interact with bone cells. Under the direction of Dr. Iwaniec, I will learn about breast cancer and bone physiology and gain laboratory experience. I will benefit Dr. Iwaniec by assisting her in performing the research. It is my understanding that the study I will be working on was funded by a small grant from the Department of Defense. If my results support the hypotheses that elevated bone turnover increases the risk for cancer metastasis to bone and/or increases cancer growth in bone, thedata will be used to justify future applications for grant support. Therefore, this proposed research collaboration combines a network of people, skills, and equipment that provides an invaluable opportunity to enhance my education through experience and in turn help my sponsor, Dr. Iwaniec.

My academic activities include pursuance of a degree in Nutrition to ultimately become a Registered Dietitian. I also am pursuing a minor in Exercise Physiology, and intend to pursue a M.S. in Nutrition. I am very interested in the way that both nutrition and exercise affect the body, and recognize that there is much to be learned through research. My goal is to use my knowledge and experience to improve the lives of others. Becoming part of this research team would provide an invaluable experience that would further my learning in an environment that could not otherwise be mirrored. The knowledge gained would not only further my learning of nutrition and its relationship to the body, but equip me with skills to pursue further research. I believe my passion for the material, and role as a student pursuing a career in the health profession make me a worthy candidate for the Life Scholars award.

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