Background: Osteosarcoma strikes hundreds of people each year, of both advanced and younger ages, and is often terminal. Like many tumor types, these bone tumors will frequently undergo a neuroendocrine transition, utilizing autocrine and/or paracrine hormones as growth factors and/or promoters of angiogenesis to facilitate progression and metastasis. While many of these factors and their actions on tumor growth are characterized, some tumor-derived neuropeptides remain unexplored.
Methods: Using validated canine osteosarcoma cell lines in vitro, as well as cells derived from spontaneous tumors in dogs, we explored the autocrine production of two neuropeptides typically found in the hypothalamus, and most closely associated with reproduction: gonadotropin-releasing hormone (GnRH) and kisspeptin (Kiss-1). We evaluated gene expression and protein secretion of these hormones using quantitative RT-PCR and a sensitive radioimmunoassay, and explored changes in cell proliferation determined by MTS cell viability assays.
Results: Our current studies reveal that several canine osteosarcoma cell lines (COS, POS, HMPOS, D17, C4) synthesize and secrete GnRH and express the GnRH receptor, while COS and POS also express kiss1 and its cognate receptor. We have further found that GnRH and kisspeptin, exogenously applied to these tumor cells, exert significant effects on both gene expression and proliferation. Of particular interest, kisspeptin exposure stimulated GnRH secretion from COS, similarly to the functional relationship observed within the neuroendocrine reproductive axis. Additionally, GnRH and kisspeptin treatment both increased COS proliferation, which additionally manifested in increased expression of the bone remodeling ligand rankl within these cells. These effects were blocked by treatment with a specific GnRH receptor inhibitor. Both neuropeptides were found to increase expression of the specific serotonin (5HT) receptor htr2a, the activation of which has previously been associated with cellular proliferation, suggesting that production of these factors by osteosarcoma cells may act to sensitize tumors to circulating 5HT of local and/or enteric origin.
Conclusions: Here we report that kisspeptin and GnRH act as autocrine growth factors in canine osteosarcoma cells in vitro, modulating RANKL and serotonin receptor expression in a manner consistent with pro-proliferative effects. Pharmacological targeting of these hormones may represent new avenues of osteosarcoma treatment.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379937 | PMC |
http://dx.doi.org/10.1186/s12885-019-5363-4 | DOI Listing |
Vet Comp Oncol
January 2025
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Colorado, Fort Collins, US.
Body composition measurements (BCM), obtained via computed tomography (CT), have been used as predictors of survival, tumour recurrence, and post-surgical infections in human oncology. There are no reports on using BCM to predict outcomes of dogs with cancer. Elevated BCM is hypothesised to place extra stress on bones weakened by cancer.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Appendicular central osteosarcoma (OSA) is a common and highly aggressive tumour in dogs. Metastatic disease to the lungs is common and even with chemotherapy the prognosis is generally poor. However, few cases survive well beyond reported median survival times.
View Article and Find Full Text PDFVet Sci
December 2024
Department of Anatomic Pathology, Faculty of Veterinary Medicine, 400372 Cluj-Napoca, Romania.
Canine extraskeletal osteosarcomas are mesenchymal, osteoid producing tumors that can arise in soft tissues without initial involvement of the bones. An 8-year-old intact male Beagle dog presented with anorexia, abdominal pain, intermittent vomiting and melena. The patient had a history of recurrent ingestion of cotton based-toy fragments, but no prior surgical procedures involving the abdominal cavity.
View Article and Find Full Text PDFObjective: To evaluate the clinical benefit and adverse events following outpatient intravenous (IV) ketamine-lidocaine (KL) infusions for palliation of cancer pain in dogs and cats.
Methods: Medical records from 15 years (2008 to 2023) were searched and data reviewed retrospectively. Animals were prescribed ketamine (0.
Biol Open
December 2024
Department of Pathobiology, University of Guelph, Guelph N1G 2W1, Canada.
MicroRNAs (miRNAs) are small non-coding RNA molecules that are present in all cell types and bodily fluids and are commonly dysregulated in cancer. miRNAs in cancer have been studied by measuring levels in cell lines, tumour tissues, and in circulation; however, no study has specifically investigated miRNA expression in patient-matched samples across all three sample types. Canine osteosarcoma is a well-established spontaneously occurring model of human osteosarcoma for which matched samples are available.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!