Publication: Tracking prostate carcinoma micrometastasis to multiple organs using histochemical marker genes and novel cell systems
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Date
2001
Authors
Culp, L.A. ; Holleran, J.L. ; Miller, C.J.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Studies of human prostate carcinoma (PCA)
have been hampered by only a few cell systems from
already-metastatic human disease. We have developed a
novel cell system by using tissue cultured CWR22R
cells from a xenograft of a primary tumor from a human
patient. These cells were transfected with the bacterial
lacZ gene to maximize their detection during
progression and metastasis in nude mice. LZ-CWR22R
cells are extremely stable for lacZ expression over 25
passages and metastasize to lung, liver, and bone from
the subcutis - major sites of metastasis of the human
disease. A matrigel vehicle facilitated development of
primary tumors and micrometastases in al1 organs. While
some micrometastases developed into overt metastases,
others remained as micrometastases for long periods of
time, possibly providing a model of latency of metastatic
disease. An experimental metastasis model (tail vein
injection) also generated micrometastases in lung, liver,
and bone with differing kinetics of formation and
stability. Serial sections of many individual lung
micrometastases within one hour of injection indicated
considerable heterogeneity in cellular composition (from
1 to 19 cells/site) while liver sites at later times were
comprised of only 1 or 2 cells (the size of bone sites
were comparable to those of liver). By combining use of
these histochemically-tagged PCA cell systems with
high resolution molecular analyses (laser-capture
microdissection), it will now be possible to analyze gene
expression patterns characteristic of micrometastases
developing in severa1 different organs.
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