Random and Directed Cell Migration During Breast Cancer Progression

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	CELLBIO-15

Authors

• C.H. Stuelten
• L. Liu
• M.C. Weigert
• C.A. Parent

Abstract

During malignant progression, epithelial tumor cells invade surrounding tissues and migrate to metastatic sites. However, tumor cell migration during malignant progression is poorly understood. In vitro cell migration assays mainly assess chemokine-triggered random migration (chemokinesis). Recently, time-lapse imaging has allowed accurate analyses of chemokinesis as well as directed tumor cell migration in a chemokine gradient (chemotaxis). We established conditions to study chemokinesis and chemotaxis in invasive, lung colony forming breast cancer cells (MCF10CA1a) and analyzed their migratory response to EGF, LPA-, and TGF-beta1. Uniform stimulation of MCF10CA1a cells with EGF increased migratory speed of cells and decreased directional movement, while LPA did not influence migratory speed but increased directionality. In EZTaxiscan chemotaxis assays, EGF mainly induced chemokinesis of MCF10CA1a cells, while LPA and TGF-beta1 gave rise to robust chemotaxis in a concentration-dependent fashion. Our results demonstrate that EGF, LPA, and TGF-beta1 differentially regulate the migration of MCF10CA1a cells. We will now study chemoattraction and chemokinesis in response to different ligands in a series of increasingly malignant breast cancer cells (MCF10A series) with the goal to identify key targets that control invasive and metastatic tumor disease.

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