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Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

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Abstract

Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity.

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Abbreviations

AML:

Acute myelogenous leukemia

CAM:

Cell adhesion molecule

EC:

Endothelial cells

ECM:

Extracellular matrix

ESC:

Endometrial stromal cell

ER:

Estrogen receptor

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

HIF:

Hypoxia-inducible factor

HPC:

Hematopoietic progenitor cell

LEL:

Large extracellular loop

LOH:

Loss of heterozygosity

MM:

Multiple myeloma

TEM:

Tetraspanin-enriched microdomain

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Acknowledgments

This work was supported by NIH grant CA096991, AHA grant 13GRNT17040028, and OCAST grant HR13-207 to XAZ, and NIH 1U54GM104938 to JDW. XAZ is an Oklahoma TSET Cancer Research Scholar. We thank Ms. Kathy Kyler for English editing. Due to page limitations, we have cited the research articles published in and after 2006. For most studies published before 2006, we have cited Liu WM and Zhang XA, Cancer Letters, 2006, 240:183–194, and references can be found therein.

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    1. Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

      Jin Feng & Dao-Wen Wang

    2. Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Sciences Center, BRC 1474, 975 NE 10th Street, Oklahoma City, OK, 73104, USA

      Chao Huang & Xin A. Zhang

    3. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

      Jonathan D. Wren

    4. Institute for Marine Biosystem and Neurosciences, Shanghai Ocean University, Shanghai, China

      Jizhou Yan

    5. Department of Biochemistry, Nanjing Medical University, Nanjing, China

      Jiexin Zhang, Yujie Sun & Xiao Han

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    Jin Feng, Chao Huang and Jonathan D. Wren contributed equally to this work.

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    Feng, J., Huang, C., Wren, J.D. et al. Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity. Cancer Metastasis Rev 34, 619–633 (2015). https://doi.org/10.1007/s10555-015-9585-x

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