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Expression of proteolytic enzymes in head and neck cancer-associated fibroblasts. 2004

Eben L Rosenthal, and Allison McCrory, and Melissa Talbert, and William Carroll, and J Scott Magnuson, and Glenn E Peters
Department of Surgery, Division of Otolaryngology--Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL 35249, USA. eben.rosenthal@ccc.uab.edu

OBJECTIVE To elucidate tumor-stromal interactions during tumor invasion by assessing the expression of proteolytic enzymes by carcinoma-associated fibroblasts (CAFs) in vivo using complementary DNA (cDNA) array analysis. METHODS Tumor-associated stroma was isolated from tumor and adjacent mucosal specimens of the same patient by laser capture microdissection, and the messenger RNA (mRNA) was assessed by cDNA microarray specific for proteolytic enzymes and their inhibitors. Protein overexpression was then analyzed by immunoblotting of primary fibroblast isolates derived from skin, mucosa, and tumor specimens. RESULTS Array analysis of 4 tumor and 4 adjacent mucosal samples demonstrated significant (2.6-fold) overexpression of membrane type 1 matrix metalloproteinase (MT1-MMP) but not of serine proteases or other matrix metalloproteinases. Analysis of normal dermal fibroblasts, normal mucosal fibroblasts, and CAFs similarly demonstrated up-regulation of MT1-MMP. CONCLUSIONS These results suggest that MT1-MMP mRNA is specifically up-regulated in CAFs in vivo whereas MT1-MMP protein is specifically up-regulated in CAFs in vitro. Known to induce tumor cell invasion when expressed in tumor cells, CAF expression of MT1-MMP may be important in the stromal response to tumor cells that characterizes the desmoplastic reaction.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D009055 Mouth The oval-shaped oral cavity located at the apex of the digestive tract and consisting of two parts: the vestibule and the oral cavity proper. Oral Cavity,Cavitas Oris,Cavitas oris propria,Mouth Cavity Proper,Oral Cavity Proper,Vestibule Oris,Vestibule of the Mouth,Cavity, Oral
D009061 Mouth Mucosa Lining of the ORAL CAVITY, including mucosa on the GUMS; the PALATE; the LIP; the CHEEK; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous EPITHELIUM covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Buccal Mucosa,Oral Mucosa,Mucosa, Mouth,Mucosa, Oral
D009960 Oropharynx The middle portion of the pharynx that lies posterior to the mouth, inferior to the SOFT PALATE, and superior to the base of the tongue and EPIGLOTTIS. It has a digestive function as food passes from the mouth into the oropharynx before entering ESOPHAGUS. Oropharynxs
D010447 Peptide Hydrolases Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES. Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D002294 Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed) Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast

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