The overexpression of the drug-efflux molecular pump P-glycoprotein (P-gp)
may confer to tumor cells the multidrug resistant (MDR) phenotype, which is
one of the causes of cancer chemotherapy failure. By investigating several
in vitro models of human tumor cells, we observed that Pgp, in addition to
its localization on the plasma membrane, can also be found intracellularly
. In particular, by using immunocytochemical and cytofluorimetric methods,
we revealed that in MDR breast cancer cells (MCF-7) a significant level of
P-gp was expressed in the Golgi apparatus, which is the major site of accum
ulation of the antitumoral compound doxorubicin. Moreover, we demonstrated
the intracellular location of P-gp in three stabilized human melanoma cell
lines which had never undergone cytotoxic drug treatment and did not expres
s the transporter molecule on the plasma membrane. Double immunofluorescenc
e labelling and immunoelectron microscopy revealed, also in this tumor cell
type, the location of P-gp in the Golgi apparatus where it seems to play a
pivotal role in intracellular drug transport. Finally, we analyzed the exp
ression, localization and function of drug transport proteins in human colo
n carcinoma lines (LoVo) exhibiting different degrees of intrinsic or drug-
induced resistance. We found that only MDR LoVo cells expressed P-gp on the
plasma membrane while both low-level drug resistant clonal LoVo cells and
MDR LoVo cells appeared to be positive for intracellular P-gp.
Our findings suggest a functional role of the intracytoplasmic P-gp in the
transport and sequestration of drugs. This represents a complementary prote
ctive mechanism of tumor cells against cytotoxic agents.