In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-04-30)
Abstract:
Epithelial tissue is one of the four major types of tissue found in animals, and is the only type of tissue that is able to form and maintain layers of cells that are just one cell thick. These layers provide inner linings to various cavities and hollow organs throughout the body—including the lungs and glandular organs such as mammary glands. A single-cell layer of epithelium is separated from the tissues beneath it by a supporting substance called the extracellular matrix. The individual cells within a single-cell layer are physically attached to the matrix, and when displaced from it, they promptly undergo programmed cell death. This mechanism preserves the single-cell layer pattern throughout the body and prevents epithelial cells from growing in inappropriate locations. It is estimated that up to 90% of cancers in humans originate in epithelial tissue, and the cells within such tumors are known to survive and divide even when they are no longer attached to the extracellular matrix. Understanding how cancerous cells gain this ability may lead to new approaches to stopping tumor cells from dividing and colonizing tissues around the body. To address this problem, Pavlova et al. explored which genes enable epithelial cells from the human mammary gland to grow without being attached to the extracellular matrix. They found that the gene that codes for a protein called poliovirus receptor-like 4 (PVRL4) allows attachment-free cell growth and also makes cells cluster together once detached from the matrix. Normally, the PVRL4 gene is not active in breast epithelial cells, but its activity is detected in many breast, lung, and ovarian tumors. Moreover, cancerous cells tend to cluster together when they are detached from the extracellular matrix. This behavior is particularly evident in the cells that divide aggressively to form tumors that subsequently migrate and colonize other tissues around the body. When Pavlova et al. used genetic techniques to silence PVRL4 in cells from breast tumors, they found that it reduced the formation of clusters by the cancer cells and also reduced their ability to grow in the absence of attachment. Pavlova et al. also showed that interactions between the PVRL4 in one cell and a related protein called PVRL1 in a neighboring cell were responsible for holding the cells together in clusters. Moreover, PVRL4 triggers a form of signaling between the cells called integrin β4 signaling that allows them to survive without being anchored to the extracellular matrix. Finally, Pavlova et al. found that injecting anti-PVRL4 antibodies (mouse proteins that attach to PVRL4 and prevent the formation of clusters) slows down the growth of breast tumors in mice. These findings suggest that inhibiting PVRL4 action with antibodies can be used as a new approach to the treatment of breast, lung, and ovarian cancers in humans.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.00358.001
DOI:
10.7554/eLife.00358.002
DOI:
10.7554/eLife.00358.003
DOI:
10.7554/eLife.00358.004
DOI:
10.7554/eLife.00358.005
DOI:
10.7554/eLife.00358.006
DOI:
10.7554/eLife.00358.007
DOI:
10.7554/eLife.00358.008
DOI:
10.7554/eLife.00358.009
DOI:
10.7554/eLife.00358.010
DOI:
10.7554/eLife.00358.011
DOI:
10.7554/eLife.00358.012
DOI:
10.7554/eLife.00358.013
DOI:
10.7554/eLife.00358.014
DOI:
10.7554/eLife.00358.015
DOI:
10.7554/eLife.00358.016
DOI:
10.7554/eLife.00358.017
DOI:
10.7554/eLife.00358.018
DOI:
10.7554/eLife.00358.019
DOI:
10.7554/eLife.00358.020
DOI:
10.7554/eLife.00358.021
DOI:
10.7554/eLife.00358.022
DOI:
10.7554/eLife.00358.023
DOI:
10.7554/eLife.00358.024
DOI:
10.7554/eLife.00358.025
DOI:
10.7554/eLife.00358.026
DOI:
10.7554/eLife.00358.027
DOI:
10.7554/eLife.00358.028
DOI:
10.7554/eLife.00358.029
DOI:
10.7554/eLife.00358.030
DOI:
10.7554/eLife.00358.031
DOI:
10.7554/eLife.00358.032
DOI:
10.7554/eLife.00358.033
DOI:
10.7554/eLife.00358.034
DOI:
10.7554/eLife.00358.035
DOI:
10.7554/eLife.00358.036
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3