Significance of sphingosine kinase 1 expression in feline mammary tumors

Abstract

Background Sphingosine kinase 1 (SPHK1) is an enzyme that converts pro-apoptotic ceramide and sphingosine into anti-apoptotic sphingosine-1-phosphate. There is growing evidence that SPHK1 activation promotes oncogenic transformation, tumor growth, chemotherapy resistance, and metastatic spread. High SPHK1 expression has been associated with a poor prognosis in several human cancers. Results In the present study, the expression level of SPHK1 was examined in feline mammary tumor (FMT) specimens, and the IHC expression level of SPHK1 was associated with the histological grade of FMTs. IHC analysis of 88 FMT cases revealed that the expression level of SPHK1 was upregulated in 53 tumor tissues (60.2%) compared to adjacent mammary tissues. SPHK1 expression in FMTs was significantly associated with histological grade, presence of lymphovascular invasion, and estrogen receptor negativity. Treatment of primary FMT cells with SPHK1 inhibitors reduced cell viability, indicating that SPHK1 acts to promote FMT cell survival. These results indicate that SPHK1 may play an important role in FMTs and may be a therapeutic target in cats with FMT. Conclusions SPHK1 over-expression in breast cancer tissues is associated with a poor prognosis in humans. SPHK1 over-expression in more aggressive FMTs provides support for a potential role of SPHK1 inhibitors for the treatment of FMTs. Targeting SPHK1 has potent cytotoxic effects in primary FMT cells. These findings suggest that further examination of the role SPHK1 plays in FMTs will pave the way for the investigation of SPHK1 inhibitors in future clinical applications. Electronic supplementary material The online version of this article (10.1186/s12917-019-1883-z) contains supplementary material, which is available to authorized users.

Intratumoral collagen signatures predict clinical outcomes in feline mammary carcinoma

“…Finally, sphingosine kinase-1 (SPHK1) was found to be increased in FMT vs normal mammary tissue, and levels within primary tumors correlated with grade, lymphovascular invasion, and ER negativity. However, while SPHK1 was shown to predict poor prognosis in human, this association was not confirmed in FMT [51]. While future studies may identify additional prognostic biomarkers for FMT, this study suggests not only the importance of specific collagen signatures in the pathogenesis of FMT but also their potential place in a prognostic panel to better serve patients with FMT as well as to identify targets to improve clinical care of these and other species with malignant mammary tumors in a comparative oncology approach.…”

Identifying novel sphingosine kinase 1 inhibitors as therapeutics against breast cancer

“…It has been observed that SphK1, a kinase that generates S1P, is highly elevated in multiple carcinomas including breast carcinoma 14 . The expression level of SphK1 was examined in feline mammary tumour specimens and found that SphK1 plays an important role in feline mammary tumours and may be used as therapeutic target 68 . Targeting SphK1 in triple-negative MDA-MB-231 breast cancer cells decreased proliferation and survival by compromising protein kinase C activity and cytokinesis 69 .…”

Serum metabolomic analysis of feline mammary carcinomas based on LC-MS and MRM techniques

“…Currently, most research on feline mammary carcinoma has focused on the role that one substance plays in carcinoma development ( 2 , 4 , 6 , 7 , 12 ). In addition, there are few studies on the metabolic changes associated with the carcinomas.…”

“…PCA score diagram in NEG mode and POS mode In the figure, the ellipse represents the 95% confidence interval, and the abscissa PC[1] and ordinate PC[2] represent the score of the principal component ranking first and second, respectively. The scatter shapes and colours represent the different experimental groups…”