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The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Tight Junctions01:29

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Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
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Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Related Experiment Video

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Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
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Tight Junctions and the Tumor Microenvironment.

Ellaine Salvador1, Malgorzata Burek1, Carola Y Förster1

  • 1Department of Anesthesia and Critical Care, University of Wurzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany.

Current Pathobiology Reports
|August 23, 2016
PubMed
Summary

Tight junctions (TJs) are crucial for cell adhesion in epithelial cancers. Their reduced expression in tumors is linked to increased cancer metastasis, highlighting their role in the tumor microenvironment.

Keywords:
CancerIntercellular permeabilityMetastasisTight junctionsTumor microenvironment

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Area of Science:

  • Cell Biology
  • Oncology
  • Biochemistry

Background:

  • Tight junctions (TJs) are specialized cell membrane structures essential for epithelial and endothelial cell adhesion and interaction.
  • Most cancers originate from epithelial cells, making the role of TJs in cancer metastasis a significant area of study.
  • The tumor microenvironment (TME) is increasingly recognized for its influence on cancer progression and metastasis.

Approach:

  • This review synthesizes current literature on the role of tight junctions in the tumor microenvironment.
  • The approach focuses on understanding how TJ integrity and expression influence cancer cell adhesion and dissociation.
  • Analysis includes findings related to TJ expression levels in highly metastatic cancer cells.

Key Points:

  • Intactness of primary tumors, particularly in epithelium-derived cancers, is influenced by intercellular structures and cell-to-cell adhesion.
  • Disruptions in these adhesion factors can lead to tumor dissociation and subsequent metastasis.
  • A notable observation is the reduced expression of tight junctions in highly metastatic cancer cells.

Conclusions:

  • Tight junctions play a critical role in maintaining tumor integrity and preventing metastasis.
  • Dysregulation of tight junctions is a key factor in cancer progression and the development of metastatic disease.
  • Further research into the mechanisms of TJ dysregulation is necessary for developing novel therapeutic strategies against cancer.