Ba. Teicher et al., REVERSAL OF IN-VIVO DRUG-RESISTANCE BY THE TRANSFORMING GROWTH-FACTOR-BETA INHIBITOR DECORIN, International journal of cancer, 71(1), 1997, pp. 49-58
Transforming growth factor-beta (TGF-beta) has been implicated in the
in vivo resistance of the EMT-6/CTX and EMT-6/CDDP murine mammary tumo
rs. Both of these tumors have a higher number of intratumoral vessels
than the EMT-6/parent tumor. Animals bearing the resistant tumors have
higher plasma levels of TGF-beta than animals bearing the parent tumo
rs; however, upon treatment with cytotoxic therapies there is a greate
r rise in plasma TGF-beta levels in animals bearing the parent tumor t
han in animals bearing the resistant tumors. In site hybridization for
TGF-beta mRNA and immunohistochemical staining for TGF-beta protein s
howed that the resistant tumor levels of this growth factor are higher
than those of the parent tumor prior to treatment; however, after cyt
otoxic therapy the increase in TGF-beta is greater in the parent tumor
than in the resistant tumors. Treatment of tumor-bearing animals with
the naturally occurring TGF-beta inhibitor decorin did not alter the
sensitivity of the parent tumor to cyclophosphamide or to CDDP as dete
rmined by tumor cell survival assay. However, administration of decori
n increased the sensitivity of the EMT-6/CTX tumor to cyclophosphamide
and of the EMT-6/CDDP tumor to CDDP so that the drug resistance of th
ese tumors was nearly ablated. A similar pattern was observed in the d
rug response of the bone marrow granulocyte-macrophage colony-stimulat
ing factor of animals bearing each of the 3 tumors. (C) 1997 Wiley-Lis
s, Inc.