Expression of haptoglobin-related protein and its potential role as a tumor antigen.

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Abstract
These studies describe the detection of a haptoglobin species, its characterization as the HPR gene product, and its association with both pregnancy and neoplasia. Previous work showed that the early recurrence of human breast cancer correlated with immunohistochemical staining with a commerical antiserum ostensibly directed against pregnancy-associated plasma protein A (PAPP-A). Use of this antiserum to guide purification of the putative antigen led to the present identification and purification of a strongly immunoreactive protein species distinct from PAPP-A that was present in the plasma of pregnant women at term. Unlike PAPP-A a homotetramer of 200-kDa polypeptides, the immunoreactive protein consists of a light (.alpha.) chain (16.5 kDa) and a heavy (.beta.) chain (40 kDa); protein microsequenching of the .beta. chain showed it to be a member of the hepatoglobin family. The .alpha. chain of this haptoglobin species differs from ordinary haptoglobin 1 and 2 .alpha. chains both structurally and immunologically and represents the product of the HPR gene, haptoglobin-related protein (Hpr), since (i) the apparent molecular mass is the same as that predicted for Hpr .alpha. chain, (ii) the peptide map differs from that of haptoglobin 1 in a manner predicted by the HPR nucleotide sequence, (iii) monospecific antibodies that react with epitopes shared by the unique .alpha. chain and a synthetic peptide derived from the HPR nucleotide sequence do not detect these epitopes in either haptoglobin 1 or 2, and (iv) sequences of .alpha.-chain peptides were consistent with this identification, excluding haptoglobin 1 but not haptoglobin 2. The immunohistochemical reactivity of antibodies raised to the synthetic Hpr peptide is similar to that of anti-PAPP-A. Moreover, staining of neoplastic breast tissue is abolished by preincubation with purified Hpr.