An In Vitro Model System for Studying Development of Human Preneoplastic Breast Disease

Case ID:
99-471

This technology is a novel model/assay system that recapitulates in vitro the in vivo processes that lead to breast cancer development and progression from preneoplastic tissue.  This model is the first that demonstrates in vitro the de novo development and neoplastic conversion of functional alveolar units.

 

Background & Unmet Need:

Although there is experimental evidence supporting the involvement of angiogenesis in pathogenesis of breast cancer, the exact nature and effects of interaction between human breast epithelial cells, also known as mammary epithelial cells, and endothelial cells have not been described thus far.  Analysis of such cell interactions requires a culture/assay system that permits growth and differentiation of both epithelial cells and endothelial cells.  The present invention provides such a system and is a model for studying the progress of preneoplastic lesions to cancer and is useful for testing the activity of agents that can inhibit this process.

 

Technology Description:

The model system comprises a co-culture of (a) preneoplastic breast epithelial cells, (b) endothelial cells, and (c) breast fibroblasts on a reconstituted basement membrane.  The co-culture is in medium containing effective concentrations of growth factors and additives that act on the epithelial and endothelial cells, along with effective concentrations of an estrogen such that the cells undergo morphogenesis, which results in the formation of a multicellular three-dimensional network of branching ductal alveolar units in culture within 3-7 days.  The cells used are preferably human cells.  This novel assay will have a wide range of applications in evaluating mechanism activity and functionality of new and existing drugs/agents that are used for chemoprevention and/or treatment of breast cancer.  The assay will have major applications in not only screening/evaluating new drugs, but also in re‑establishing and re-evaluating known drugs:  i.e., drugs that selectively inhibit angiogenesis and thus block neoplastic conversion, drugs that directly inhibit alveolar morphogenesis by acting on epithelial cells, drugs that induce terminal differentiation thus inhibiting neoplastic conversion, and drugs that inhibit proteolytic enzymes because these enzymes are key to invasion and transformation to malignancy.

 

Commercial Applications:

  • Use in high throughput drug screening
  • Re-establishing and re-evaluating known drugs used for breast cancer treatment

 

Stage of Development:

Preclinical; cellular studies performed

 

Competitive Advantages:

  • Requires only 7 days of morphogenesis compared to 8-10 days in vivo

 

Intellectual Property Status:

Patent issued

 

Related Publications or Citations of Work:

Interaction with endothelial cells is a prerequisite for branching ductal-alveolar morphogenesis and hyperplasia of preneoplastic human breast epithelial cells: regulation by estrogen.  Shekhar MP, Werdell J. Tait L., Cancer Res. 2000 Jan 15: 60(2): 439-49.

Preneoplastic mammary epithelial-endothelial cell interactions:  Regulation by estrogen.  P.V.M. Shekhar, J. Werdell, S. Wolman, and L. Tait.  Proc. AACR, 40:2733, April 1999

 

Patent Information:
For Information, Contact:
Joan Dunbar
Associate Vice President for Technology Commercialization
Wayne State University
(313) 577-5542
jcdunbar@med.wayne.edu
Inventors:
Malathy Shekhar
Larry Tait
Keywords:
Assay
Breast Cancer