Background

The matrix metalloproteinases (MMP) are a group of zinc dependent enzymes (endopeptidases) which degrade varying components of the extracellular matrix in both normal and diseased tissue. Some of the functions are summarized in the table below.

ROLE OF MMP IN PHYSIOLOGIC AND PATHOLOGIC PROCESS	CHARACTERIZATION
Embryogenesis and development	Controlled proteolytic activity and extracellular matrix remodelling occurs during implantation and normal embryonic development
Acute wound healing	MMP1 and MMP10 are expressed by basal keratinocytes at the migrating wound front MMP3 is expressed by distinct group of keratinocytes behind this migrating front
Cancer and metastasis	MMP7 may play a role in tumor progression and has been demonstrated in cancers of the colon, pancreas, transitional cell carcinomas of the kidney, and small cell carcinomas of the lung MMP may contribute to tumor growth by facilitating development of angiogenesis allowing extravasation of tumor cells-may involve MMP1, 2, 9, and MT1-MMP with serine proteases
Cutaneous tumors	In basal cell carcinoma, MMP1, 2, 9, 11 protein and mRNA have been demonstrated in stromal cells adjacent to the tumor Invasive squamous cell carcinomas are associated with expression of MMP 1 and 10
	J Biol Chem 1999;274:21056-21062 Melanoma has been associated with MMP-2 with expression associated with the degree of cellular atypia-also highly invasive melanoma cell lines produce significantly lower amounts of TIMP-2 than do lesser invasive ones, suggesting more proteolytic activity in the invasive cells
Chronic wounds	MMP 1 and 3 are in higher levels
Bullous diseases	Bullous pemphigoid shows distinct expression profile with MMP9 mRNA limited to eosinophils and capable of cleaving the extracellular portion of the 180 kd BP autoantigen
Noninfectious granulomatous disease	Sarcoidosis, granuloma annulare, and necrobiosis lipoidica show similar profile of MMP9 and 12 MMP2 localized to stromal fibroblasts
Photodamage	Increased MMP1,3,7,9, and 12 have been found in sun-exposed skin
Contact hypersensitivity	MMP 3 necessary for initiation of the response and MMP 9 required to clear the eruption

The families of MMP are continually being catalogued. The following compilation is the most recent classification.

MMP	OTHER NAMES
1	Collagenase 1, interstitial collagenase
2	Gelatinase A, 72kD gelatinase
3	Stromelysin 1
7	Matrilysin, PUMP
8	Collagenase 2, neutropil collagenase
9	Gelatinase B, 92kD gelatinase
10	Stromelysin 2
11	Stromelysin 3
12	Macrophage metalloelastase
13	Collagenase 3
14	MT1-MMP
15	MT2-MMP
16	MT3-MMP
17	MT4-MMP
18	Collagenase 4
19	No other name
20	Enamelysin
21	XMMP
22	CMMP
23	No other name

MPPs are not constitutively expressed. The activity of MMP is regulated by the following:

Gene expression via cytokines, growth factors, and cell-cell and cell-matrix interactions
Activation of the proenzyme or zymogen form
Natural inhibitors including tissue metalloproteinase inhibitors (TIMPs)

There is a tightly regulated balance between these enzymes and inhibitors. Disease processes result when this balance goes awry. Recently synthetic inhibitors are in clinical trials as possible anti-cancer agents.

TISSUE INHIBITORS OF METALLOPROTEINASES	CHARACTERIZATION
TIMP-1
TIMP-2
TIMP-3
750 kd protein
16.5 kd protein
Marimastat (BP-2516)	Synthetic inhibitor Currently in trial as an anti-angiogenic agent
Primomastat (AG3340)	Synthetic inhibitor Specific inhibitor of MMP2, 13, and MT-MMP

Adv Dermatol 2000;16:185-208
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Skin

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

• Pathologists Who Make A Difference
• Search for a Physician Specialist

Last Updated 1/5/2004

Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.

Copyright © The Doctor's Doctor