Almost all tumor cells found in the bone marrow of early stage breast cancer patients appear to be breast cancer stem cells, suggesting the risk of disease spread for all breast cancer patients may be greater than previously thought, according to a ground-breaking study by Richard J. Cote, professor of pathology and urology at the Keck School of Medicine.
The study, “Most Early Disseminated Cancer Cells Detected in Bone Marrow of Breast Cancer Patients Have a Putative Breast Cancer Stem Cell Phenotype,” which appears in this week’s issue of Clinical Cancer Research, provides the first evidence of the putative stem/progenitor cells within tumor cells collected from the bone marrow.
Stem cells are a type of cell in breast tumors that are believed to seed the growth of new cancers. These cells are only a small part of the vast number of cells within tumors, but they can act like adult stem cells�a basic cell that can grow into different types of specialized cells.
Current research has focused on the theory that it is these stem cells landing in a distant site that create metastases, and not simply single cells that detach from the primary tumor and travel to another part of the body.
Although disseminated tumor cells, either in the bone marrow or lymph nodes, are already regarded as a prerequisite for relapse and metastasis, no studies have as yet examined these cells for the existence of the stem cell phenotype.
“The primary implication is that it is the stem cell population in cancers that are presumed to be the only cells capable of forming metastases,” said Cote. “Metastasis is the most important event for determining outcome in cancer patients.
In the study, Cote and colleagues looked at 50 bone marrow specimens from women whose breast cancer was caught in its earliest stages, but in whom tumor cells were detected in the bone marrow. Using a newly developed immunohistochemical protocol, Cote and colleagues found the tumor cells from all patients contained a population of putative stem cells.
The presence of the CD44 protein the absence of the CD24 protein defines the stem cell population of tumor cells. Only a small proportion of tumor cells at the primary site (in the breast) have been shown to have the stem cell characteristics. It has been shown that only the stem tumor cells have the ability to form metastases in experimental models.
What was surprising to Cote and his colleagues, who anticipated some stem cells within the disseminated tumor cells, was that the majority of tumor cells have the stem cell characteristics, and that they appeared in the bone marrow of breast cancer patients whose disease was caught in the earliest stages.
“We know that the presence of disseminated tumor cells in the bone marrow is a bad feature, as it is an indicator of future metastases, but we didn’t know if these were the cells that actually cause disease progression,” said Cote. “These data suggest that the vast majority of patients with disseminated tumor cells may have a life-time risk for relapse. We definitely need to pursue molecular studies of these putative stem cells.”
The study was funded by a grant from the National Cancer Institute.
Marija Balic, Henry Lin, Lillian Young, Debra Hawes, Armando Giuliano, George McNamara, Ram H. Data, Richard J. Cote, “Most Early Disseminated Cancer Cells Detected in Bone Marrow of Breast Cancer Patients Have a Putative Breast Cancer Stem Cell Phenotype,” Clinical Cancer Research, Oct.1, 2006, Volume 12, Num 19, 5615-5621.