Increased Expression of the 25-Hydroxyvitamin D3-1α-Hydroxylase Gene in Alveolar Macrophages of Patients with Lung Cancer

Abstract

25-Hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase) plays a central role in calcium metabolism by synthesizing the active hormone 1alpha,25-dihydroxyvitamin D(3) in the kidney. Its increased expression in the extrarenal tissues has been found in alveolar macrophages in sarcoidosis but not in any other pathological conditions. We found that 1alpha-hydroxylase-mRNA in alveolar macrophages measured by semiquantitative RT-PCR was 2-fold greater in patients with lung cancer than in control subjects (0.61 +/- 0.20 vs. 0.34 +/- 0.11, respectively; P < 0.0001). When the clinical stages of lung cancer were divided into early (stage IA-IIIA) and advanced (stage IIIB and IV) and the expression of 1alpha-hydroxylase gene was compared among the control, early, and advanced groups, the advanced group showed the highest expression, followed by the early group, then the control group (0.34 +/- 0.11, 0.52 +/- 0.11, and 0.69 +/- 0.23 for control, early, and advanced groups, respectively; P < 0.0001). The 1alpha-hydroxylase-mRNA level was well correlated with serum 1alpha,25-dihydroxylase D(3) concentration and the 1alpha,25-dihydroxylase D(3) to 25-hydroxyvitamin D(3) ratio, but none of the findings related to calcium metabolism among the patients with lung cancer. Increased local production of 1alpha,25-dihydroxyvitamin D(3) may be associated with the pathological conditions, such as immunosuppression, in lung cancer.

Autocrine Metabolism of Vitamin D in Normal and Malignant Breast Tissue

“…The underlying basis for up-regulation of 1a-hydroxylase in breast tumors is also clear, but we have observed a similar induction of 1a-hydroxylase in lymphomas (37) and dysgerminomas (48). In these cases, synthesis of 1,25(OH) 2 D 3 was mediated via expression of 1a-hydroxylase in tumor-associated macrophages, and a similar pattern of increased expression of 1a-hydroxylase has also been reported in alveolar macrophages associated with lung cancer (49). It was therefore interesting to note the immunolocalization of 1a-hydroxylase in the inflammatory infiltrate of breast tumors, suggesting that this cell type may be the source of at least some of the 1,25(OH) 2 D 3 in breast tumors.…”

Season of Diagnosis and Survival of Advanced Lung Cancer Cases - Any Correlation?

“…They concluded that a subset of lung cancer patients may be susceptible to the differentiating effects of vitamin D analogues. Later Yokomura et al (2003) found higher levels of 1 alpha hydroxylase activity in alveolar macrophages of lung cancer patients when compared with control group. In subgroup analysis, in advanced stage cases (IIIB and IV) the expression of 1 alpha hydroxylase gene was the highest, followed by early stage and then the control group.…”

Cancer survival is dependent on season of diagnosis and sunlight exposure

“…Recent studies have reported 1a-hydroxylase expression in the prostate, breast and colon and thus the ability of these cells to locally synthesize 1,25(OH) 2 D which can then exert its antiproliferative and antimetastatic effects in an autocrine or paracrine fashion. [27][28][29][30][31] There is evidence that this extrarenal production is not subject to the tight regulation present in the kidneys. Mortality hazard ratios also adjusted for cumulative mean sunlight hours during 1 month before diagnosis.- 4 Mortality hazard ratios also adjusted for cumulative mean sunlight hours during 3 months before diagnosis.- 5 Mortality hazard ratios also adjusted for cumulative mean sunlight hours during 6 months before diagnosis.- 6 Mortality hazard ratios also adjusted for cumulative mean sunlight hours during 9 months before diagnosis.…”