October 1 Cancer Research Highlights

Women who have borne children have a reduced risk for breast cancer, but the basis for this effect is not entirely clear. Fetal cells, including stem cells that can contribute to microchimerism, are known to enter the circulation during normal pregnancy. Prompted by the hypothesis that this process could affect tumoral immune surveillance, perhaps through recognition of oncofetal antigens, the authors found that fetal microchimerism was more frequent in healthy women than in women with breast cancer. If these findings can be extended, they may offer one explanation for why parity lowers breast cancer risk in women.

One trend in studies of cell cycle regulatory proteins is their connections to cell migration. This study reports that cytosolic localization of p27^Kip1 in melanoma, which occurs commonly, is associated with an oncogenic function that drives metastasis. Further studies of this function may provide novel insights into the regulatory integration of cell division and malignant invasion in cancer.

Inflammatory cytokines such as CCL2 have been widely implicated in tumor cell invasion and migration. While the specific role played by CCL2 is not entirely clear, it has been implicated in recruiting macrophages to help drive angiogenesis and metastatic colonization, in particular, to bone. Prostate tumors often metastasize to bone. In assessing the effects of antibody-mediated depletion in a mouse model of prostate cancer, Loberg and colleagues found that neutralizing antibodies to CCL2 could elicit tumor regression. These findings suggest that CCL2 antibodies may be useful in prostate cancer treatment.

TRAIL and Multikinase Inhibitor Sorafenib Cooperate to Enhance Cancer Cell Death

Sorafenib, originally identified as a Raf inhibitor but later shown to act as a nonspecific kinase inhibitor, has been approved for the treatment of renal cell carcinoma. Studies of the cytotoxic action of this compound in leukemia cells revealed that it can potentiate TRAIL-mediated cancer cell death. Mechanistic investigations traced this effect of Sorafenib to down-regulation of Bcl2-related protein Mcl-1 and TNF pathway mediator cFLIP_L. These findings may help leverage the potential use of these agents for the treatment of leukemia and other cancers.

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Correcting Dietary Calcium Insufficiency May Benefit Metastatic Breast Cancer Patients

Breast cancers often metastasize to bone. High bone turnover has been associated with metastatic spread, but direct evidence has been lacking. Dietary calcium affects bone turnover but breast cancer patients are often deficient in dietary calcium. In this study, the authors examined the effects of dietary calcium on bone turnover in a model of breast cancer growth in bone. The findings, which demonstrated more aggressive growth under calcium-deficient conditions, suggest that dietary regimens to correct calcium insufficiency may be useful in the adjuvant or palliative settings of metastatic breast disease. 

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