Objective—To screen for expression of 9 predominant
members of the matrix metalloproteinase
(MMP) family, including membrane-type matrix metalloproteinases
(MT-MMPs) and tissue inhibitors of
metalloproteinases (TIMPs), in primary tumor tissue
biopsy specimens of vaccine site-associated sarcomas
(VSS) in cats and compare expression profiles of
VSS with expression profiles of non-VSS and carcinomas.
Procedure—Tissue specimens were obtained from
primary tumor biopsy specimens of cats. Primers for
reverse transcriptase-polymerase chain reaction
assay were designed on the basis of known
sequences. Data were analyzed for patterns of
expression of MMPs, MT-MMPs, and TIMPs.
Differences in expression patterns were evaluated
among cats of differing genders, ages, metastasis
status, and overall survival durations, and between
cats with VSS and cats with non-VSS tumor types.
Results—A total of 31 primary tumor tissue biopsy
specimens and 6 nontumor (normal) tissue biopsy
specimens were screened for the presence of 6
MMPs and 3 TIMPs. Matrix metalloproteinase and
TIMP expression was found in non-VSS, carcinomas,
and VSS. No significant differences were found in patterns
of expression among tumor types. Metastasis
was found to be the only predictive factor for overall
survival duration. A significant correlation was found
between MMP2 and MT-MMP16 expression and
overall duration of survival.
Conclusions and Clinical Relevance—The identification
of MMPs in feline VSS supports an underlying
inflammatory pathogenesis for this tumor. Expression
of MMP2 and MT-MMP16 were correlated with survival
time in our study. ( Am J Vet Res 2004;
Objective—To detect, isolate, and characterize feline
stromelysin-1 (ie, matrix metalloproteinase [MMP]-3)
in naturally developing tumors in cats.
Sample Population—31 tissue samples obtained
from primary tumors and 6 samples of normal tissues
Procedure—Biopsy specimens were obtained from
primary tumors. Primers were designed on the basis
of known sequences. The sequence of stromelysin-
1 was cloned and analyzed. An additional primer set
was used as a screening tool. Samples were
assayed in duplicate or triplicate, when possible.
Data obtained were analyzed for differences in
expression of stromelysin-1 with regard to overall
survival among cats of various sex, age, and disease
Results—A 1,181-bp cDNA nucleotide sequence was
amplified. The open reading frame encoded 393 amino
acids. This amino acid sequence shared 70% to 85%
sequence homology with sequences of other species.
In addition, samples were screened for stromelysin-1.
Of the 31 tumor samples tested, 16 (51.6%) had positive
results for expression of stromelysin-1. Total RNA
expression was detected in a diverse group of tumor
types. Prognostic factors associated with a shorter
duration of survival included evidence of metastasis and
metastasis associated with expression of stromelysin-1.
Conclusions and Clinical Relevance—Feline
stromelysin-1 contains all the conserved regions typically
found in members of the MMP family. Activity of
stromelysin-1 has been implicated in a wide number
of physiologic and pathologic processes. Identification
of this gene may lead to the development of useful
reagents to assist with diagnosis and management of
neoplastic diseases in cats. (Am J Vet Res 2004;
Objective—To isolate and characterize the cDNA
sequence of canine stromelysin-1 (matrix metalloproteinase
[MMP]-3), screen various naturally developing
primary tumors of dogs, and assess the effect of
stromelysin-1 on survival of dogs with cancer.
Sample Population—3 canine cell lines and biopsy
specimens of primary tumors collected from 54 dogs.
Procedure—3 canine cell lines and biopsy specimens
of primary tumors collected from 54 dogs at the
University of Illinois Veterinary Teaching Hospital were
used in the study. Primer sets based on human
stromelysin-1 and consensus sequences were
designed for expression, screening, and isolation. Two
additional primer sets were designed for screening.
Samples were assayed at least in duplicate. Data
were analyzed for differences in expression of
stromelysin-1 on the basis of sex, age, metastasis,
malignant versus nonmalignant tissue origin, and
duration of patient survival.
Results—A 1,479-bp cDNA nucleotide sequence was
amplified from established canine cell lines. The open
reading frame encoded a protein consisting of 478
amino acids. This sequence was 70% to 88% homologous
with stromelysin-1 of other species at the
amino acid level. Fifty-four samples were screened
for stromelysin-1. Of these, 34 (63%) had positive
results and 20 (37%) had negative results for expression.
Stromelysin-1 and metastasis were associated
with a poor prognosis for survival.
Conclusions and Clinical Relevance—Stromelysin-1
is a potential activator of other members of the MMP
family. Additional studies are needed to investigate
the relationship between stromelysin-1 production
and aggressive biological behavior of tumors in dogs.
(Am J Vet Res 2005;66:1526–1535)