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LPA stimulates ovarian cancer cell surface uPA/uPAR activity
Author(s) -
Lundt Anastasia,
Henningsen Meghan,
Gardner Nicole,
Miller Geoff,
Heying Emily,
Farley Janean,
Liu Yueying,
Stack Sharon,
Ellerbroek Shawn
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.707.8
We found lysophosphatidic acid (LPA) stimulated matrigel invasion of ovarian cancer (OVCA) cells through a uPA‐dependent process. We therefore analyzed the effects of LPA on the expression and distribution of uPA and its cell surface receptor, uPAR, at both early (2–4 hr) and late (36 hr) time points. After 2 hours, uPA secretion was stimulated nearly two‐fold. uPAR expression and uPA cell surface binding were unchanged, although uPAR underwent dramatic surface redistribution by immunofluorescence (junctional or aggregate). Inhibition of uPA with a function‐blocking antibody did not impact E‐cadherin junction breakdown. After 36 hrs of LPA‐stimulation, E‐cadherin junctions still exhibited dissolution and uPA secretion was either non‐existent or minor when normalized to the positive effects of LPA on cell density. At the same time, LPA promoted significant binding of uPA to OVCA cell surfaces through a process involving PI3K signaling. In support, uPAR expression was increased following 36 hrs of LPA treatment. Together, these data support involvement uPA/uPAR cell surface activity in LPA‐stimulated ovarian cancer invasion. This work was supported by the RJ McElroy Trust.