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The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis

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Pathology Oncology Research

Abstract

Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.

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Abbreviations

NH2-terminal:

Amino-terminal

CA19-9:

Carbohydrate Antigen 19-9

CEA:

Carcinoembryonic Antigen

CSF:

Cerebrospinal Fluid

EC:

Endothelial Cell

ECM:

Extracellular Matrix

HDMVEC:

Human Dermal Microvascular Endothelial Cell

HUVEC:

Human Umbilical Vein Endothelial Cell

IL-1α:

Interleukin-1 Alpha

IL-1β:

Interleukin-1 Beta

IL-8:

Interleukin-8

IVVM:

Intravital Videomicroscopy

MMP:

Matrix Metalloproteinase

MMPI:

Matrix Metalloproteinase Inhibitor

MT-MMP:

Membrane-Type Met-alloproteinase

PMA:

Phorbol 12-Myristate 13-Acetate

PMNs:

Polymorphonuclear Cells

TSP-1:

Thrombospondin-1

TIMP:

Tissue Inhibitor of Metalloproteinase

TGF-β:

Transforming Growth Factor Beta

TNF:

Tumor Necrosis Factor

VEGF:

Vascular Endothelial Cell Growth Factor

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  1. Department of Pathology, Medical College of Pennsylvania and Hahnemann University School of Medicine, Philadelphia, USA

    Anitha John & George Tuszynski

  2. Department of Surgery, Medical College of Pennsylvania and Hahnemann University School of Medicine, Philadelphia, USA

    George Tuszynski

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  1. Anitha John
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  2. George Tuszynski
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Correspondence to George Tuszynski.

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John, A., Tuszynski, G. The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol. Oncol. Res. 7, 14–23 (2001). https://doi.org/10.1007/BF03032599

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