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3D-Tissue Culture Reveals New Targets for Cancer Therapy

Posted by admin | Posted in 3D Cell Culture | Posted on 20-09-2010

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3D-Tissue Culture Reveals New Targets for Cancer Therapy (from National Cancer Institute)

Over the past few years, research has shown clearly that tumor cells behave differently when allowed to grow in three dimensions rather than simply in two dimensions on the surface of a culture dish.  Indeed, now that cancer biologists have developed several methods for reproducibly growing malignant cells in three dimensions, they are finding new approaches to therapy that were not apparent from older, two-dimensional studies.

Two papers published recently in the journal Cancer Researchhighlight the value of mastering three-dimensional cell culture techniques.  In one paper, Catherine Park and her colleagues at the Lawrence Berkeley National Laboratory and the University of California, San Francisco, demonstrate that a cell adhesion molecule known as α5β1integrin enables breast cancer cells to survive radiation therapy.  More importantly, they then showed a small peptide can prevent α5β1-integrin from binding to the protein fibronectin, which in turn heightens the cell killing effects of radiation.

Integrins are a family of molecules that play a critical role in how cells bind to and interact with one another.  In this study, Dr. Park and her collaborators were able to show that malignant cells growing in three-dimensional culture greatly overproduced α5β1 integrin after radiation treatment.  At the same time, using gene expression data from 295 breast cancer patients, the investigators found that elevated expression of the α5β1 integrin gene was associated with poor survival, suggesting that inhibitors of α5β1 integrin could prove useful in boosting the efficacy of radiation therapy in human breast cancer patients.

In a second, unrelated paper, Anil Rustgi and his colleagues from the University of Pennsylvania describe a series of experiments using three-dimensional cell culture techniques that show that a different cell adhesion molecule, known as periostin, boosts the invasiveness of esophageal tumors.  With this information in hand, the investigators then examined gene expression data from human esophageal cancer patients and found that primary invasive esophageal cancer has a distinct profile that differs from adjacent normal human esophageal tissue. With further study, these findings could be useful both in the search for new therapeutic targets and for developing a prognostic indicator for esophageal cancer.

The study on breast cancer sensitivity to radiation therapy, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Breast Cancer Cells in Three-dimensional Culture Display an Enhanced Radioresponse after Coordinate Targeting of Integrin α5β1 and Fibronectin.”  An abstract of this paper is available at the journal’s Web site.
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The study on tumor invasion, which was supported in part by the National Cancer Institute,  is detailed in a paper titled, “Periostin, a Cell Adhesion Molecule, Facilitates Invasion in the Tumor Microenvironment and Annotates a Novel Tumor-Invasive Signature in Esophageal Cancer.”  An abstract of this paper is available at the journal’s Web site.
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