A novel thrombospondin-1 variant as a potential diagnostic biomarker and therapeutic target in canine mammary tumor and osteosarcoma cells.

Abstract

Importance: Thrombospondin-1 (TSP1) is a vital glycoprotein that plays a key role in critical biological functions, including cell migration, invasion, angiogenesis, and proliferation. Understanding the roles of its variants, particularly TSP1 variant (TSP1V), is critical for cancer biology and therapy.

Objective: This study examined the expression of the transcriptional variant TSP1V, focusing on canine TSP1 sequences.

Methods: The expression of canine TSP1 sequences was analyzed using a reverse transcription polymerase chain reaction (RT-PCR) to identify the TSP1 wild-type (dTSP1W) and novel canine TSP1V transcripts (dTSP1V). The effects of damnacanthal and genistein, anticancer compounds, on the viability of canine mammary and osteosarcoma cell lines were assessed by modulating the expression ratios of TSP1V to TSP1W at the transcriptional level. RT-PCR analysis compared the relative dTSP1V and dTSP1W concentrations in normal and tumor canine mammary tissues.

Results: Two dTSP1V were identified. Treatment with damnacanthal and genistein decreased cell proliferation in canine mammary and osteosarcoma cell lines, associated with changes in the TSP1V to TSP1W expression ratio. RT-PCR analysis revealed increased dTSP1V expression in normal tissues, while dTSP1W expression was elevated in tumor tissues.

Conclusions and relevance: TSP1V may be a potential diagnostic biomarker and therapeutic target for mammary tumors and osteosarcoma in dogs. The differential expression of dTSP1V and dTSP1W in normal versus tumor tissues underscores the importance of TSPIV in cancer biology, expanding the understanding of its role beyond human thyroid cancer and laying the groundwork for future research in other cancers and species.