Discoveries thrust cancer-initiating stem cells into a larger role in cancer biology and treatment

>The two genes appear to influence stem cell self-renewal by controlling two different arms of the pathway, says Korkaya. In breast cancer, the loss of PTEN is linked to nearly a quarter of all cases, while the overproduction of HER2 is associated with nearly 40 percent of all cases. Patients with a combined defect of PTEN loss and HER2 amplification represent worse prognosis than either defect alone.

To replicate this clinical phenomenon and study the link between stem cell self-renewal and tumorigenesis, the researchers altered the expression of the two genes in a line of human breast carcinoma cells. In experimental settings, their results confirmed this clinical data that either defect increases stem cell population by three to five times. Furthermore, Korkaya observed an additive effect and an approximate 10-fold increase in stem cell population when they created a cell line with deleted PTEN and HER2 overexpression. Another property of aggressive tumors is metastasis; the team also found that these cells had increased invasive capacity in a matrigel invasion assay.

"In general, tumors are heterogeneous including stem and non-stem cell populations in a given malignancy," Korkaya said. "If the stem cells acquired mutations in their self-renewing pathways, they will then begin reproducing at an accelerated rate, leading to a particularly aggressive form of cancer."

The researchers believe further studies will identify new biomarkers that will enable physicians to clinically screen patients for mammary stem cells and provide specific treatments designed to target these cells.

Local Radiotherapy Might Contribute to Leukemia Risk in Breast Cancer by Recruitment of Hematopoietic Stem Cells: Abstract 5050

Radiation therapy affects not only the cancer mass, but also the surrounding tissues, including the bone marrow. Signals from the cells in the bone marrow damaged by cancer radiotherapy could be involved

Contact: Staci Vernick Goldberg
American Association for Cancer Research

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