International Journal of Cell Cloning, Vol 1, 2-14, Copyright © 1983 by AlphaMed Press
Potential therapeutic and diagnostic applications of the growth of testicular cancer in soft agar
BJ Foster, N Javadpour and RF Ozols
Sixteen histologically documented testicular cancer specimens obtained at
diagnostic procedures following induction chemotherapy with cis- platinum
containing regimens were cloned in soft agar. Seven (44%) of the specimens
cultured formed colonies with a mean cloning efficiency of .021%. Colony
formation was observed with all the common histologic subtypes of
testicular cancer (seminoma, embryonal carcinoma, choriocarcinoma and mixed
tumors). In vitro drug sensitivity tests were performed using cis-platinum,
vinblastine and VP-16. Three of four specimens demonstrated a decrease in
colony formation to less than 50% of controls after a 1 h exposure to VP-16
at 300 micrograms/ml. Two of these patients had a response to treatment
with a VP-16 based salvage regimen. Immunoperoxidase staining of the
colonies for alpha feto protein and human chorionic gonadotropin were
correlated with the serum levels of these tumor markers determined at the
time the specimen was obtained. In three instances the same markers were
elevated in the serum as detected within cells which formed the colonies;
however, in two other cases the marker(s) that was elevated in the serum
was not expressed in the colonies. In one case a biopsy of a residual
retroperitoneal mass following chemotherapy histologically was a teratoma,
but it formed colonies in the assay which stained positive for alpha feto
protein. This patient subsequently developed an elevated serum alpha feto
protein. These studies have demonstrated that (a) testicular cancer can be
cloned directly in soft agar; (b) a heterogeneous tumor cell population
exists in metastatic testicular cancer specimens; and (c) a dose response
exists for VP-16 in relapsed testicular cancer which suggests that
increasing the dose of VP-16 may be clinically beneficial.
