In female B6D2F1 mice bearing an MXT-M-3,2
breast cancer graft the level of the phagocytic cells (e.g. of granulocytes and macrophages in the spleen and of granulocytes and monocytes in the blood) is significantly elevated. The positive correlation between the number of the phagocytic cells and the weight of the
tumor indicates that the MXT-M-3,2
breast cancer promotes myelopoiesis, presumably by secretion of hematopoietic
growth factors like
GM-CSF. This process can be described for each phagocyte type by a regression equation. Due to its hormonal potency [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)
ethylenediamine] dichloroplatinum(II) (meso-1-PtCl2) can reduce the excessive numbers of the granulocytes and macrophages, which seem to be responsible for the progressive growth of the MXT-M-3,2
breast cancer. This process leads to an interruption of the vicious circle of mutual growth stimulation of
breast cancer cells and these phagocytes. The target of
meso-1-PtCl2 is the
estrogen receptor (ER) of the
breast cancer cell. The interaction between
meso-1-PtCl2 and the ER presumably results in a diminished secretion of hematopoietic
growth factors and hence in a decline of the number of phagocytic cells.
Meso-1-PtCl2 does not inhibit the proliferation of
tumor cells by direct interaction with their
DNA, as is described for
platinum complexes like cDDP. In its mode of action the equipotent,
breast cancer inhibiting
drug cDDP differs from
meso-1-PtCl2. This is obvious from the fact that in cDDP--but not in meso-1-PtCl2-treated,
tumor bearing mice the number of granulocytes and macrophages does not markedly deviate from that in untreated control mice with
tumors of the same weight. The
drug cDDP probably does not interfere with the mechanism of the secretion of hematopoietic
growth factors. The reduction of the number of
tumor cells by cDDP leads to a decline of the number of phagocytic cells in accordance with the respective regression equations. In contrast to
meso-1-PtCl2 and cDDP,
ovariectomy causes elevated phagocyte numbers, probably due to the strongly reduced
estrogen level. The studies described in this publication indicate that the anti-
breast cancer activity of
meso-1-PtCl2 is caused by a decimation of phagocytes and with this by an abolition of the
tumor promoting effect. Furthermore, a restoration of the natural immunosurveillance seems to be of importance.