Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study.

Cancer-Associated Fibroblasts (CAFs) are crucial in genesis and progression of tumors; however, cervical CAFs (C-CAFs) are not well characterized. Estradiol (E2) has been implicated as a cofactor in human papillomavirus (HPV)-mediated cervical cancer (CxCa), both in animal models and in women using oral contraceptives; however, the exact role of the hormone is unclear. Human C-CAFs have recently been shown to express estrogen receptor alpha (ER-α). We investigated gene expression patterns in ex vivo cultured early and late stage C-CAFs in the context of E2. CAFs were isolated from four patients with early and two patients with late stage CxCa. ER-α expression in CxCa tissues was localized to stromal fibroblast-like cells and confirmed in ex vivo cultured C-CAFs. Two ER antagonists (ICI 182,780 and Methyl Piperidino Pyrazole) were used to unravel ER signaling in CAFs. Microarray technology was used for expression profiling and validated by quantitative reverse transcription PCR. The transcriptomes of C-CAFs across stages indicated their activated state. C-CAFs had gene expression patterns associated with both pro-tumorigenic and pro-inflammatory signaling. Late-stage C-CAFs compared to those of early stage appeared to be more actively metabolizing and cycling but expressed fewer genes related to immune function. We report differential expression profiles between C-CAFs: early vs. late stage and in the presence of ER antagonists. Both ER antagonists seemed to modulate C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression. This study characterized C-CAFs from early and late stage disease, and experiments with ER inhibitors emphasized the probable importance of canonical ER-α signaling. Interfering with paracrine signaling through fibroblast ER-α is worth exploiting as a targeted therapy in CxCa management.

Relative role of olfactory cues and certain non-olfactory factors in foraging of fruit-eating bats.

The proportion of captivated Indian short-nosed fruit bats, Cynopterus sphinx, approaching fruits within a specified duration and the fruit-approaching latency were recorded under various test conditions (involving variations in the olfactory and certain aspects of the physical environment, and the time of food presentation). While alterations in the majority of physical features in the immediate environment of bats failed to affect either of the foraging parameters studied, one or both of them were markedly influenced by the presence of light or source of a novel odour, or a delay of 24 h in the regular feeding time. When paper pieces coated with homogenized fruit pulp were provided instead of the fruit pieces during the regular feeding time, bats responded normally; they, however, did not approach water-wetted papers. Initially the bats did not consume grapes. However, following the supply of grapes coated with homogenate of banana fruits, grapes were approached and consumed in considerable quantities. The results underscore that light has a crucial role in the foraging activity of C. sphinx and they rely extensively on olfactory cues to detect the fruits. In another experiment the bats were daily provided simultaneous access to two adjacent fruit-containing cages; fruits in one of the cages were accessible but those in the other cage were not. Cedar wood oil, source of a strong odour, was placed in either of the cages. Observations revealed that the bats can learn to associate the availability of fruits with the presence of an odour within 3 days.