Some cancer secret a growth factor which attracts stem cells
that promote the growth of the cancer cells.
Stem cell role in breast cancer
Cancer Uses Growth Factors to Lure Stem Cells
Like a siren song, breast cancer secretes growth factors to attract stem cells then uses those cells - which normally promote
healing - to help it survive, researchers have found.
In the laboratory, the researchers have documented secretion of growth factors FGF2 and VEGF by breast cancer cells,
seen these factors bind to receptors on stem cells then watched stem cells migrate toward the cancer. When they took the growth
factors away, the deadly migration decreased. These stem cells are there to make normal tissue; they make fat, cartilage,
bone," says Dr. Adam Perry, general surgery resident at the Medical College of Georgia. "But if you have a tumor, it will
in a sense mimic some tissue type to get the cells to come and help form the environment that is called the tumor stroma that it needs to get beyond
a certain size. That's really
when cancer becomes clinically problematic."
Knowing how tumors attract the stem cells they need to thrive opens up new avenues for earlier detection, better staging
and more targeted therapies, he says. Dr. Perry's work on this fatal attraction between cancer and adult bone marrow stem
cells earned him the Peter J. Gingrass, M.D. Memorial Award for the best paper presented by a medical student or non-plastic
surgery resident during the recent 50th anniversary meeting of the Plastic Surgery Research Council. "When you have a growing tumor, the tumor cells cannot stand alone," says Dr. Edmond Ritter, MCG plastic
surgeon and senior co-investigator. "Tumors have specific colon cancer or breast cancer or melanoma cells, but they also have
to have supporting framework which includes fibroblasts as well as blood vessels."
Normally, FGF2 makes connective tissue and VEGF makes blood vessels. It was known that tumors contain these growth
factors as well as others and that they utilize stem cells to help build the infrastructure they need. "We wanted to figure
out what attracts these stem cells," says Dr. Perry. "What makes them move?" "You
need blood vessels. You need other tissue that forms basically a home or a nest for the tumor," says Dr. Erhard Bieberich,
MCG biochemist and senior investigator. "Without that, you don't get metastasis. Without the activity of those stem cells,
metastasis would only grow to a particular size but it would not be life-threatening. But once the body response kicks in
and accepts the metastasis as some sort of useful tissue, it really gets dangerous." The
MCG researchers hypothesized that growth factors secreted by tumors cells might play a role in this acceptance.
Dr. Bao-Ling Adam, a cancer researcher and proteomics expert, helped measure levels of FGF2 and VEGF - both proteins
- using a high-tech approach that enables evaluation of hundreds of proteins at one time. Cells
need protein to survive and cells normally keep some proteins they make and shed others, Dr. Adam says. Much as a blood test
can show what proteins are being secreted in the body, the researchers looked in the cell culture media where the cancer cells
resided to see what proteins were being secreted. "We wanted to see what kind
of molecules are released in the media and then what molecules attract stem cells," says Dr. Adam. They are still working
to identify other molecules that were secreted, but FGF2 and VEGF were definite standouts. "In
the case of breast cancer, FGF2 and VEGF meet the criteria as candidate molecules and we believe they have an important role
but are not the only answer as to why stem cells migrate," says Dr. Ritter, who specializes in reconstruction following mastectomy. The researchers say different kinds of tumors likely send out different growth factors to lure stem
cells. In fact, they've already
shown that melanoma also uses VEGF but not FGF2. "You don't want to treat every tumor alike," says Dr. Ritter.
They believe knowing the factors that help lead stem cells astray is an important first step in stopping the deadly
attraction. "The first generation of chemotherapy was more targeting the cell division of cancer," says Dr. Bieberich. "Now
we are entering a new phase where we are targeting more the communication pathways." Possibilities include using antibodies
or other small molecules to block growth factor receptors or even turning the tables on cancer by arming stem cells with a
mechanism to kill the cancer once they connect, he says.
Dr. Perry has seen the need for options other than chemotherapy, radiation therapy or surgery in his relatively short
professional life. "What we are doing now is looking at more precise, specific ways to treat cancer on cellular level. This
requires an immense understanding of tumor biology and what is going on. We are trying to chip away at that puzzle." Dr. Perry is just completing a year of research in the laboratories of Drs. Bieberich
and Adam. He plans to pursue a plastic surgery fellowship after completing his surgery residency.
A significant part of the initial work for these studies was conducted by Kathryn Tucciarone, who worked as a research
assistant in Dr. Bieberich's lab. Dr. Jack Yu, chief of the Section of Plastic and Reconstructive Surgery, and Dr. Thomas
N. Wang, surgical oncologist, also supported the studies.
Medical College of Georgia