PI Eric Lagasse
Title Metastatic Colon Cancer, Stem Cells, and Artificial Bioreactors
Summary This study will focus on the cellular characterization of metastatic colon cancer in the liver and a 3-D perfusion culture instrument that recapitulates hepatic vasculature and microenvironment. Colon cancer is a very common cancer second only to lung cancer. Distant metastases are one of the worst prognostic signs as this places the patient in the most advanced staging category. Colon cancers generally spread through the lymphatics or through the portal venous system to the liver. The liver is the most frequent visceral site of metastatic dissemination and is the initial site of distant spread in one-third of recurring colon cancers, with two-thirds of patients having liver involvement at the time of death. The median survival after the detection of distant metastases range from 6 to 9 months (with heavy liver involvement) to 24 to 30 months (with initially small liver nodules).
Our hypothesis, based on the current cancer stem cells model, is that metastatic colon cancer of the liver is a clonogenic event initiated by cancer stem cells which are optimally adapted to proliferate under the prevailing conditions in the primary tumor and emerges to form the metastatic cancer. Our goal will be to characterize the cancer cells isolated from metastatic colon cancer in the liver by identifying the cancer-initiating cell leading to the metastatic tumor and determine if this cell have the characteristic of a stem cell.
Finally, we propose to reconstitute in vitro tumor growth environment similar to what is found in patient affected with metastatic colon cancer using artificial liver bioreactors.
The specific aims pertaining to the main goal and its hypotheses are listed below:
Aim 1: Identification of colon cancer stem cells.
Aim 2: Expansion of human metastatic colon cancer stem cell populations using bioreactors.
Our approach will be to integrate the fields of stem cell biology, cancer biology, tissue engineering, and clinical treatment of patients to develop promising new therapies for patients with metastatic colon cancer. The overall goal of this project is to use cancer stem cells to create a diagnostic bioreactor using a novel 3-D culture model, which would allow tumor cells to recapitulate their in vivo geno- and phenotype diversity. This “in vitro” regeneration of the patient tumors in bioreactors would allow a new individualized chemotherapy planning and the discovery of novel approaches to effectively target cancer stem cells.
Source American Association for Cancer Research; AACR Grants in Metastatic Colon Cancer Research
Term 07/01/06 – 06/30/08
