Vitamin D, Th17 Lymphocytes, and Breast Cancer.

Vitamin D3, which is well known to maintain calcium homeostasis, plays an important role in various cellular processes. It regulates the proliferation and differentiation of several normal cells, including immune and neoplastic cells, influences the cell cycle, and stimulates cell maturation and apoptosis through a mechanism dependent on the vitamin D receptor. The involvement of vitamin D3 in breast cancer development has been observed in numerous clinical studies. However, not all studies support the protective effect of vitamin D3 against the development of this condition. Furthermore, animal studies have revealed that calcitriol or its analogs may stimulate tumor growth or metastasis in some breast cancer models. It has been postulated that the effect of vitamin D3 on T helper (Th) 17 lymphocytes is one of the mechanisms promoting metastasis in these murine models. Herein we present a literature review on the existing data according to the interplay between vitamin D, Th17 cell and breast cancer. We also discuss the effects of this vitamin on Th17 lymphocytes in various disease entities known to date, due to the scarcity of scientific data on Th17 lymphocytes and breast cancer. The presented data indicate that the effect of vitamin D3 on breast cancer development depends on many factors, such as age, menopausal status, or obesity. According to that, more extensive clinical trials and studies are needed to assess the importance of vitamin D in breast cancer, especially when no correlations seem to be obvious.

Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors.

Retinol-binding protein 4 (RBP4) is proposed as an adipokine that links obesity and cancer. We analyzed the role of RBP4 in metastasis of breast cancer in patients and in mice bearing metastatic 4T1 and nonmetastatic 67NR mammary gland cancer. We compared the metastatic and angiogenic potential of these cells transduced with Rbp4 (4T1/RBP4 and 67NR/RBP4 cell lines). Higher plasma levels of RBP4 were observed in breast cancer patients with metastatic tumors than in healthy donors and patients with nonmetastatic cancer. Increased levels of RBP4 were observed in plasma, tumor tissue, liver, and abdominal fat. Moreover, the blood vessel network was highly impaired in mice bearing 4T1 as compared to 67NR tumors. RBP4 transductants showed further impairment of blood flow and increased metastatic potential. Exogenous RBP4 increased lung settlement by 67NR and 4T1 cells. In vitro studies showed increased invasive and clonogenic potential of cancer cells treated with or overexpressing RBP4. This effect is not dependent on STAT3 phosphorylation. RBP4 enhances the metastatic potential of breast cancer tumors through a direct effect on cancer cells and through increased endothelial dysfunction and impairment of blood vessels within the tumor.