Pathological and functional significance of Semaphorin-5A in pancreatic cancer progression and metastasis

Oncotarget
Sugandha SaxenaRakesh K Singh

Abstract

Semaphorin-5A (SEMA5A) has differential cell surface expression between normal and cancer cells and represents an attractive target for therapeutic intervention in pancreatic cancer (PC). In this study, we delineated the pathological expression and significance of SEMA5A during PC progression and metastasis. We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras(G12D), Pdx1-Cre; LSL-Kras(G12D); LSL-p53(R172H)and RIP1-Tag2) to analyze SEMA5A expression during PC progression. Using human patients and different mouse models, we demonstrated that SEMA5A expression was highest in liver metastases, followed by primary pancreatic tumors, and the lowest expression was found in the normal pancreas. SEMA5A expression was localized on tumor cells with no staining in the surrounding stroma. To understand the functional significance of SEMA5A, we treated PC cell lines with recombinant SEMA5A. We observed an increase in migration, chemotaxis, and scattering of PC cells. To delineate the signaling axis of SEMA5A, we generated SEMA5A receptor-Plexin-B3 knockdown in T3M-4 and CD18/HPAF PC cell lines and observed that the effect of SEMA5A treatment was absent in the Plexin-B3 knockdown counterparts of T3M-4 and C...Continue Reading

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Citations

Sep 24, 2019·Current Pharmaceutical Biotechnology·Konrad DziobekDariusz Boroń
Dec 4, 2019·International Journal of Oncology·Pin-Hao KoLiang-Chuan Lai
Dec 24, 2018·BMC Cancer·Sugandha SaxenaRakesh K Singh
Nov 21, 2018·Journal of Experimental & Clinical Cancer Research : CR·Simona D'AguannoDonatella Del Bufalo
Sep 10, 2020·Cytokine & Growth Factor Reviews·Damon Fard, Luca Tamagnone

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Datasets Mentioned

BETA
GDS4103

Methods Mentioned

BETA
xenograft

Software Mentioned

NIH ImageJ
GraphPad
PanNET
GraphPad Prism
Image J

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