When breast cancer spreads, the disease typically invades the long bones of the body, such as the femur and tibia. Inside these long bones, giant marrow cells known as megakaryocytes (or MKs) go into overdrive in the presence of cancer and may contribute to destructive bone loss and embolisms.
In a healthy person, says Penn State graduate student Walter Jackson, MKs are responsible for producing the platelets needed for normal blood clotting, but in the course of certain diseases, including metastatic cancer, their number increases nearly ten-fold.
"The breast cancer survival rate is about 90 percent when it's detected early but drops considerably lower once the cancer has spread to the bones," says Jackson. There hasn't been enough research on how these specialized bone marrow cells affect the spread of cancer cells, in spite of the fact that many cancer patients die of thromboembolism, or blood clots, he notes. "It's important that we learn more about bone metastasis and how to slow it down."
Under the guidance of Professor of Microbiology and Cell Biology Andrea Mastro, Jackson is working to tackle this problem head on. His thesis research project, "The Role of Megakaryocytes in Breast Cancer Metastasis to Bone," has resulted in a published paper (co-authored with Mastro and colleagues) and in his selection as winner of the 2013 Robert T. Simpson Graduate Award for Innovative Research award from the Department of Biochemistry and Molecular Biology.
A Bridge to the Doctorate
A native of Shreveport, Louisiana, Jackson graduated as his high school's (Huntington High) valedictorian in 2003 before continuing on as a biology major -- and football player -- at Alcorn State University in Mississippi. Alcorn State is the oldest public historically black land-grant institution in the United States and is also the alma mater of Jackson's parents.
After receiving his bachelor's degree in biochemistry in 2007, Jackson entered the Alcorn State: Penn State University Bridges to the Doctorate Program, a National Institutes of Health-funded collaboration between the two institutions, with additional funds provided by Penn State's Huck Institutes of the Life Sciences.
The program, designed to foster underrepresented students' matriculation directly into Penn State doctoral programs after completion of their master's degree in biological sciences from Alcorn State, was initially funded in 2006 for three years and was renewed for an additional five years.
Pamela Hankey, professor of immunology and coordinator of the Bridges program at Penn State, thinks Jackson exemplifies what the initiative can achieve. "This program is one of only fourteen Bridges to the Doctorate programs in the country and due to the hard work and dedication of students like Walter, it has been extremely successful," she says.
"I feel blessed to be a part of it," Jackson says. "I was one of the first ones in the program, so I figured I couldn't quit or fail, because I didn't want anyone else behind me to get discouraged and quit." He adds with a laugh, "I also had to prove that jocks can actually think!"
New Clues to Cancer's Spread
In fact, Jackson -- the youngest of a large, close-knit family -- has been thinking about science for a long time. "I can recall being five or six years old and telling my mom and my aunts that I wanted to cure people." The end goal of his research contributing to improved care for real patients is never far from his mind. "My aunt recently died of cancer," he shares. "I haven't taken the MCAT (Medical College Admission Test) yet but it's still a possibility."
His research on megakaryocytes was inspired by observations made in Mastro's lab. While examining sections of femurs of mice with metastatic cancer, he and his colleagues noticed that megakaryocytes seemed significantly increased in number in the marrow of those mice with cancer compared with non-tumor bearing mice.
Mastro, lead investigator on the study, explains that prior to these observations, there had been many "indirect connections" hinting that MKs might play a role in metastatic breast cancer, but no solid reports.
While their subsequent research hasn't yet cracked the entire mystery, Mastro and Jackson's results confirmed a marked increase of MK cells in the femurs of mice with breast cancer when compared to an uninoculated control group, suggesting a direct role in the spread of cancer to bone.
It is commonly accepted that cancer cells have ways of creating a microenvironment within the body that sets the stage for malignant colonization. The bone microenvironment is a complex one, explains Jackson, and includes an array of cytokines -- small signaling molecules -- and growth factors. Jackson and Mastro hypothesized that megakaryocytes contribute to growth of breast cancer cells in the bone either by preparing a niche for the cancer to grow and/or by responding to cytokines in the marrow.
Jackson notes that the interplay between cancer cells and host cells is a vicious cycle that leads to metastatic bone destruction and tumor growth. Rather than being overwhelmed by the disease's complexity, he says he's inspired to continue doing research. "There are many types of cells in the bone micro-environment," he explains, "including the resident cells such as osteoblasts, osteoclasts, stromal cells, and hematopoietic stem cells. This project made me eager to look at some of these other types of cells. In particular, I want to do human clinical research down the line."
In Mastro's view, Jackson is poised for continued success. In his recommendation letter for the Simpson Award, she wrote of her protégé, "Walter is dedicated and committed. He has taken charge of the project."
As a college football player, Jackson's position was offensive tackle. "I'm thinking now about blocking cells, not linebackers," he grins. "I want to learn more about how to block these MKs and slow the spread of metastases."
"The end goal," he says simply, "is to save lives."