Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture, and ultrastructural study.
Transferrin receptors on proliferating and malignant cells are well documented. Iron is an essential micronutrient for cell growth that plays an important role in energy metabolism and DNA synthesis. Malignant cells requiring more iron modulate a transferrin receptor. Iron-bound transferrin interacts with this receptor, facilitating the transport of iron across the cell membrane. Transferrin is a glycoprotein and is the chief iron transport protein in mammalian blood. The more aggressive the tumor, the higher the transferrin receptor levels and the greater the proliferative index. We have found by cytochemical and ultrastructural studies that ferritin, an iron storage protein, is increased in breast cancer tissue. Anaplastic tumors have higher tissue ferritin levels. Tissue ferritin concentration may be an indirect method of measuring transferrin receptors and thus might be an index of proliferation and a prognostic indicator. Transferrin may be used as a carrier to target toxic therapy selectively to tumor tissue. A platinum transferrin complex (MPTC-63) has been developed and shown to be cytostatic in tissue culture, animal, and human studies. It also sensitizes tissue to agents that produce free radicals, such as adriamycin, and thus is synergistic with other drugs and radiation. Other transferrin complexes and conjugates of gallium, indium, and daunorubicin have also shown growth inhibition in tissue culture and animals. Human studies are in progress. By studying iron metabolism in breast cancer, we may be able to selectively inhibit tumor growth without toxic effects, and with other tumor biologic data be better able to select the stage I patient for adjuvant therapy.
Elliott
R L
RL
Mastology Research Institute, Baton Rouge, Louisiana 70816.
Elliott
M C
MC
Wang
F
F
Head
J F
JF
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001940:Breast; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D004357:Drug Synergism; D005260:Female; D005293:Ferritins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009944:Organoplatinum Compounds / Q000633:toxicity; D051381:Rats; D011990:Receptors, Transferrin / Q000032:analysis / Q000378:metabolism; D014168:Transferrin / Q000032:analysis / Q000378:metabolism / Q000633:toxicity
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011990:Receptors, Transferrin; D014168:Transferrin; C057651:platinum transferrin; D004317:Doxorubicin; D005293:Ferritins; D007501:Iron