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)
Objective—To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues.
Sample Population—57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs.
Procedures—Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois.
Results—Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length.
Conclusions and Clinical Relevance—Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human antitelomerase strategies.