We reported inhibition of growth of primary rat mammary
carcinomas after infusions of
tumor-bearer plasma absorbed with
Protein A-Sepharose or inactivated CNBr
Sepharose. Absorbed plasmas were depleted of the third component of
complement (C3) (other
complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of
complement might be involved in the observed antitumor effects. To test this concept sera were treated with
ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic
acid before absorption with
Protein A-Sepharose.
Ethylenedinitrilotetraacetic acid, by chelating
calcium and
magnesium, prevents activation of both the alternative and classical
complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic
acid, by chelating
calcium but not
magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence of
chelating agent were absorbed with
Protein A-Sepharose twice at room temperature. After absorption
calcium was added to the sera. Rats were treated by i.v. injection of sera twice a week for 2 weeks. Measurements of
tumor size were made weekly for 5-7 weeks and then
tumor weight was determined. Groups were compared both for size of index and total
tumors. The results can be summarized as follows:
tumor-bearer sera before absorption did not inhibit the growth of rat primary mammary
carcinomas;
tumor-bearer sera after absorption with
Protein A-Sepharose showed significant consumption of C3 and did inhibit
tumor growth;
tumor-bearer sera absorbed in the presence of
ethylenedinitrilotetraacetic acid did not show a decrease in C3 functional activity and did not inhibit
tumor growth;
tumor-bearer sera absorbed in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic
acid did show a decrease in C3 functional activity and did inhibit
tumor growth; sera from normal adult female rats after absorption with
Protein A-Sepharose did inhibit
tumor growth. The results are consistent with a role for the alternative pathway of
complement in the inhibition of growth of rat primary mammary
carcinomas observed
after treatment with absorbed sera.