Accession Number:

ADA446352

Title:

Modulation of Anaplastic Lymphoma Kinase Upon Tumor-Stroma Interaction and Its Implications for Tumor Growth and Metastasis in Breast Cancer

Descriptive Note:

An

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

2005-09-01

Pagination or Media Count:

17.0

Abstract:

Induction of neovascularization is needed for a growing tumor as well as for its metastasis. Angiogenic and growth promoting factors like Pleiotrophin PTN act on endothelial and epithelial cells and on fibroblasts. We identified the receptor for PTN as anaplastic lymphoma kinaseALK. In individual tissues the presence of ALK is elevated in tumor stroma endothelium while adjacent normal tissue lacked ALK. In cultured endothelial cells or human fibroblasts ALK is upregulated in response to supernatants from human breast cancer cells. Our hypothesis is that ALK from stromal cells upregulated in response to factors from tumor cells, constitutes a marker and a potential therapeutic target in breast cancer. We investigated the specificity of ALK modulation in tumor stroma versus normal endothelium in response to growth factors and breast cancer cell lines supernatants. We underscored the importance of the ALKIPTN axis in migration and invasion and we blocked these effects with blocking antibodies. The completion of the study will translate in establishing ALK as a new target for the breast metastatic cancer therapy.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE