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Early Placenta Insulin-like Growth Factor (pro-EPIL) Is Overexpressed and Secreted by c-erbB-2-positive Cells with High Invasion Potential¹

Institute for Clinical Chemistry and Laboratory Medicine [B. B., K. S., J-H. M., D. K.] and Gerhard-Domagk-Institut of Pathology [W. B., H. B.], Westfälische Wilhelms-Universität Münster, Germany 48149; Genius Diagnostics, Münster, Germany [A. R.]; Departement de Biologie Clinique, Institut Gustave-Roussy, 94805 Villejuif, France [J-M. B.]; Institute of Pathology, 45000 Osnabrück, Germany [J. P.]; and Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030 [D. Y.]

By differential-display PCR a subclone of the SKBR3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of the INSL-4 gene. This new member of the insulin-like growth factor family encodes for a peptide, designated early placenta insulin-like (EPIL), being expressed in the so-called "invasive" phase of the placental development. Immunohistochemistry on tissue microarrays revealed a heterogeneous expression of EPIL in breast cancer tissue and no expression in the surrounding stroma cells. A coexpression of pro-EPIL and c-erbB-2 could be observed predominantly in cell clusters at the infiltrating edge of the tumor. Our results give new suggestions for the presence of a signaling network of receptor tyrosine kinases underlying breast cancer invasion and metastasis.

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