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Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

Emerging in vitro and in vivo data underline the crucial role of G-protein-coupled receptors (GPCRs) in tumorigenesis. Here, we report the contribution of hGPR87, a predicted member of the P2Y subfamily of GPCRs, to proliferation and survival of human tumor cell lines. hGPR87 mRNA transcript was found to be preferentially overexpressed in squamous cell carcinomas (SCCs) of different locations and in their lymph node metastases. Up-regulation of both, transcript and protein, was detected in samples of SCC of the lung, cervix, skin and head and neck (pharynx, larynx and epiglottis). In addition to the expression of hGPR87 in tumors which originate from stratified epithelia, we identified other hGPR87-positive tumor types including subsets of large cell and adenocarcinomas of the lung and transitional cell carcinomas of the urinary bladder. Loss of function studies using siRNA in human cancer cell lines lead to antiproliferative effects and induction of apoptosis. Like other known P2Y receptors, hGPR87 was found to be mainly located on the cell surface. The overexpression of hGPR87 preferentially in SCCs together with our functional data suggests a common molecular mechanism for SCC tumorigenesis and may provide a novel intervention site for mechanism-based antitumor therapies.