Mesenchymal Stem Cells Promote Mammosphere Formation and Decrease E-Cadherin in Normal and Malignant Breast Cells

Normal and malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew, referred to as stem cells, or tumor initiating cells (TIC). These cells can be enriched by growth as "mammospheres" in three-dimensional cultures.We tested the hypothesis that human bone-marrow derived mesenchymal stem cells (MSC), which are known to support tumor growth and metastasis, increase mammosphere formation.We found that MSC increased human mammary epithelial cell (HMEC) mammosphere formation in a dose-dependent manner. A similar increase in sphere formation was seen in human inflammatory (SUM149) and non-inflammatory breast cancer cell lines (MCF-7) but not in primary inflammatory breast cancer cells (MDA-IBC-3). We determined that increased mammosphere formation can be mediated by secreted factors as MSC conditioned media from MSC spheroids significantly increased HMEC, MCF-7 and SUM149 mammosphere formation by 6.4 to 21-fold. Mammospheres grown in MSC conditioned media had lower levels of the cell adhesion protein, E-cadherin, and increased expression of N-cadherin in SUM149 and HMEC cells, characteristic of a pro-invasive mesenchymal phenotype. Co-injection with MSC in vivo resulted in a reduced latency time to develop detectable MCF-7 and MDA-IBC-3 tumors and increased the growth of MDA-IBC-3 tumors. Furthermore, E-cadherin expression was decreased in MDA-IBC-3 xenografts with co-injection of MSC.MSC increase the efficiency of primary mammosphere formation in normal and malignant breast cells and decrease E-cadherin expression, a biologic event associated with breast cancer progression and resistance to therapy

Different Prey Resources Suggest Little Competition Between Non-Native Frogs and Insectivorous Birds Despite Isotopic Niche Overlap

Non-native amphibians often compete with native amphibians in their introduced range, but their competitive effects on other vertebrates are less well known. The Puerto Rican coqui frog (Eleutherodactylus coqui) has colonized the island of Hawaii, and has been hypothesized to compete with insectivorous birds and bats. To address if the coqui could compete with these vertebrates, we used stable isotope analyses to compare the trophic position and isotopic niche overlap between the coqui, three insectivorous bird species, and the Hawaiian hoary bat. Coquis shared similar trophic position to Hawaii amakihi, Japanese white-eye, and red-billed leiothrix. Coquis were about 3 ‰ less enriched in δ15N than the Hawaiian hoary bat, suggesting the bats feed at a higher trophic level than coquis. Analyses of potential diet sources between coquis and each of the three bird species indicate that there was more dietary overlap between bird species than any of the birds and the coqui. Results suggest that Acari, Amphipoda, and Blattodea made up \u3e90% of coqui diet, while Araneae made up only 2% of coqui diet, but approximately 25% of amakihi and white-eye diet. The three bird species shared similar proportions of Lepidoptera larvae, which were ~25% of their diet. Results suggest that coquis share few food resources with insectivorous birds, but occupy a similar trophic position, which could indicate weak competition. However, resource competition may not be the only way coquis impact insectivorous birds, and future research should examine whether coqui invasions are associated with changes in bird abundance