Biochemical and Biophysical Research Communications
Ephrin A5 expression promotes invasion and transformation of murine fibroblasts
Section snippets
Materials and methods
Cell culture. NIH 3T3 cells were cultured in Dulbecco’s modified Eagle’s medium supplemented with 10% cosmic calf serum (CCS) and 1% penicillin/streptomycin at 37°C in 5% CO2. Stable cell lines expressing ephrin A5, ephrin B1 or empty vector were created by transfecting 3T3 cells with pBABE-ephrin A5, pBABE-ephrin B1, or pBABE alone using FuGENE6 (Roche Molecular Biochemicals) according to the manufacturer’s instructions, followed by selection in 3 μg/ml puromycin. Stable lines were verified by
Results and discussion
Ephrins and their receptors, Ephs, form an essential cell–cell communication system capable of signalling in both forward and reverse directions [2]. Involvement of the ephrin/Eph system has consistently been demonstrated in multiple aspects of embryonic development [1]. Recent evidence also suggests that the ephrin/Eph system may play a role in metastasis, invasion, and angiogenesis [1], [4]. Examination of this new role, however, has focused on the contribution of Eph receptors, rather than
Summary
Recent studies suggest a role for the ephrin/Eph system in cancer. In lieu of the above evidence, we conclude that ectopic expression of ephrin A5 in murine fibroblasts elevates oncogenic potential, including increased invasive behaviour, anchorage-independent growth, and morphological transformation. Our results suggest that the ephrin ligands themselves, not just the Eph receptors, may play a role in tumourigenesis. Future in vivo studies are being undertaken to further explore this role.
Acknowledgments
We thank the Southern Alberta Microarray Facility, supported through a Canadian Institutes of Health Research (CIHR) Multi-user Equipment and Facilities grant, for help and guidance with the gene profiling experiments. This work was supported by an operating grant from CIHR to S.M.R. S.M.R. currently holds a Canada Research Chair in Cancer Biology and is an Alberta Heritage Foundation for Medical Research (AHFMR) Scientist. T.N.C. and S.A. were supported by AHFMR Postdoctoral Fellowships.
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Eph receptors and their ligands: Promising molecular biomarkers and therapeutic targets in prostate cancer
2013, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :These examples highlight the differences in signaling outcomes dependent on cancer cell context or presence/absence of cognate ligand. Selected examples of ephrin reverse signaling in cancer have shown that it can transform cells through Src activation and promote invasion through Rac1 [61–63]. These examples are highly simplified and representative of the complexity of Eph/ephrin signaling in cancer.
Down-regulation of ephrin-A5, a gene product of normal cartilage, in chondrosarcoma
2009, Human PathologyCitation Excerpt :As EFNA5 down-regulation may be associated with decreased cellular adhesion [5-7], it may be a potential cause of tumor spread. Because EFNA5 down-regulation has been reported for several malignant tumors, it seems doubtful whether EFNA5 overexpression, which has been associated with invasion and transformation of NIH3T3 cells [21,22], may correspond to the situation in tumors in vivo. Anyway, we conclude that invasive growth and tumor spread, which occurs in conventional chondrosarcomas of higher grade and dedifferentiated chondrosarcomas, is obviously correlated with EFNA5 down-regulation in chondrosarcomas.
Distinct membrane compartmentalization and signaling of ephrin-A5 and ephrin-B1
2008, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Microarray analysis. Microarray experiments were conducted according to Campbell et al. (2006) [17]. RNA from ephrin-A5 or ephrin-B1 transfectants or empty vector 3T3 cells was extracted by the TrizolTM method using 10:1 Trizol:sample volume ratios (Invitrogen) [19].
Eph-Ephrin Bidirectional Signaling in Physiology and Disease
2008, CellCitation Excerpt :However, the decreased tumorigenicity of cancer cells in which Eph receptor expression was experimentally decreased suggests that these receptors can also have tumor-promoting effects. The role of ephrin reverse signaling in cancer cells is poorly characterized, although several ephrins have been reported to promote cell transformation and cancer cell migration/invasion (Campbell et al., 2006; Meyer et al., 2005; Tanaka et al., 2007). To complicate matters further, the Eph system is also operational in the tumor microenvironment.
Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via Ephrin-A5
2022, British Journal of Cancer
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Present address: Resverlogix, Calgary, Alta., Canada.