Project Title

Nicotine-induced breast cancer cell migration and invasion phenotype is mediated by Ca2+-independent Phospholipase A2β

Award

Finalist: 2015 Outstanding Scientific Project

Major

Biology Pre-med

Department

Biological Sciences

Degree

Undergraduate

Mentor

Lindsay E. Calderon

Mentor Department

Biological Sciences

Abstract

Ca2+-independent Phospholipase A2β (iPLA2β) is a member of the phospholipase A2 superfamily has been linked to the regulation of a variety of cellular signaling pathways and functions. This is in part due to the catalytic activity of iPLA2β, cleaving glycerophospholipids at the sn-2 position causing the release of free fatty acids including arachidonic acid and 2-lysophospholipid. However, the ability of iPLA2β to mediate breast cancer cellular functioning including proliferation and migration remains unknown. Our central hypothesis is that suppression of iPLA2β reduces nicotine-induced breast cancer metastasis through attenuating MMP-9 (Matrix Metalloprotease-9) secretion. Our in-vivo preliminary data shows that iPLA2β is overexpressed in 4TI stage four breast cancer tumors grown in-vivo for 2 weeks and nicotine (5mg/kg/day) significantly increased growth at 2weeks and 4 weeks. Additionally, we found Bromoenol lactone, 3uM (BEL) an inhibitor of iPLA2β significantly attenuated nicotine-induced breast cancer cell proliferation. Further, we found that BEL significantly decreased nicotine-induced breast cancer cell migration (gap closure) utilizing a scratch assay. Through the use of gel zymography we elucidated that BEL attenuates nicotine-induced matrix metallopreotease-9 secretion, which, is an important contributor to cancer cell metastasis and the initiation of angiogenesis. Taken together, our in-vivo and in-vitro results indicate that iPLA2β is an important regulator of nicotine-induced breast cancer tumor growth, cell migration, and proliferation. Much work is still to be done in future studies to fully elucidate the full capacity of iPLA2β in mediating breast cancer tumerogenicity, angiogenesis, and its invasive nature. Research support by epscor NSF grant.

Presentation format

Poster

Poster Number

41

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Nicotine-induced breast cancer cell migration and invasion phenotype is mediated by Ca2+-independent Phospholipase A2β

Ca2+-independent Phospholipase A2β (iPLA2β) is a member of the phospholipase A2 superfamily has been linked to the regulation of a variety of cellular signaling pathways and functions. This is in part due to the catalytic activity of iPLA2β, cleaving glycerophospholipids at the sn-2 position causing the release of free fatty acids including arachidonic acid and 2-lysophospholipid. However, the ability of iPLA2β to mediate breast cancer cellular functioning including proliferation and migration remains unknown. Our central hypothesis is that suppression of iPLA2β reduces nicotine-induced breast cancer metastasis through attenuating MMP-9 (Matrix Metalloprotease-9) secretion. Our in-vivo preliminary data shows that iPLA2β is overexpressed in 4TI stage four breast cancer tumors grown in-vivo for 2 weeks and nicotine (5mg/kg/day) significantly increased growth at 2weeks and 4 weeks. Additionally, we found Bromoenol lactone, 3uM (BEL) an inhibitor of iPLA2β significantly attenuated nicotine-induced breast cancer cell proliferation. Further, we found that BEL significantly decreased nicotine-induced breast cancer cell migration (gap closure) utilizing a scratch assay. Through the use of gel zymography we elucidated that BEL attenuates nicotine-induced matrix metallopreotease-9 secretion, which, is an important contributor to cancer cell metastasis and the initiation of angiogenesis. Taken together, our in-vivo and in-vitro results indicate that iPLA2β is an important regulator of nicotine-induced breast cancer tumor growth, cell migration, and proliferation. Much work is still to be done in future studies to fully elucidate the full capacity of iPLA2β in mediating breast cancer tumerogenicity, angiogenesis, and its invasive nature. Research support by epscor NSF grant.