Monoclonal antibodies to human tumor nucleolar antigens: probes for studying biological function and determining clinical significance

Abstract

Using novel strategies, monoclonal antibodies (MAbs) were developed to two proliferation-associated nucleolar antigens. These two new antigens, termed P145 and P120, according to their molecular weights, were found in a broad range of tumor tissues. Overall, P120 was more restricted in its distribution than P145 because it was absent from many benign tumors and some malignant tumors. Using the MAbs as probes, antigens P145 and P120 were localized to separate nucleolar components. P145 was mainly associated with high molecular weight nucleolar RNPs. Antigen P120 was localized to a novel beaded microfibril found in a nucleolar residue fraction. DNAse and high salt treatment of this fraction provided optimal extraction of the P120 antigen. P145 and P120 differed from other proliferation-associated nuclear/nucleolar antigens identified by autoimmune sera and by other MAbs. In PHA stimulated lymphocytes, both antigens were expressed in early G1 prior to or concurrent with increased RNA Pol I transcription. Microinjection of tumor cells with the P120 MAb inhibited cell proliferation and blocked the appearance of nucleolar pleomorphism that is characteristic of tumor cells. Clinical studies showed that P145 was not detected in normal bone marrow but was expressed in leukemic marrows (AML); the percentage of P145 positive cells correlated with percentage of malignant blasts (Raza et al., Am. Soc. Hematology, 1990). Antigen P145 was detected in 10 of 39 marrows from patients in complete remission. This result suggested that these cells have a higher proliferative potential than normal stem cells.(ABSTRACT TRUNCATED AT 250 WORDS)