Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor.

Abstract

A unique structural feature of the neural cell adhesion molecule N-CAM is the presence of homopolymers of alpha (2----8)-linked sialic acid units. We have used two specific probes for the detection of poly(sialic acid) in normal human kidney and Wilms tumor: a monoclonal antibody against meningococci group B capsular polysaccharide (homopolymers of alpha (2----8)-linked sialic acid units), which shows no crossreactivity with polynucleotides and denaturated DNA, and bacteriophage-induced endosialidases specifically hydrolyzing alpha (2----8)-linked poly(sialic acid) units. Additionally, for the detection of N-CAM, antibodies recognizing the polypeptide portion of the molecule and biotinylated antisense RNA transcribed from a cDNA clone for N-CAM were applied. Poly(sialic acid) was regionally detectable in human embryonic kidney but undetectable in normal adult kidney, as already reported for rat kidney. The malignant Wilms tumor, which is characterized by the presence of structural components resembling those found in embryonic kidney, reexpressed poly(sialic acid) units and showed positive immunostaining for the polypeptide portion of N-CAM. Immunoblot analysis of Wilms tumor as well as human embryonic kidney and brain with the monoclonal anti-poly(sialic acid) antibody revealed in each case the same high molecular mass broad band. In situ hybridization demonstrated the presence of mRNA for N-CAM in Wilms tumor. We conclude that poly(sialic acid), most probably present on N-CAM, is an oncodevelopmental antigen in human kidney.

Biochemical Engineering of Surface α2–8 Polysialic Acid for Immunotargeting Tumor Cells

“…The samples that had tumor cells were scored positive and were subjected to semiquantification by serial dilution. although polysialic acid is ubiquitous on fetal tissue, it is only found in a few discrete adult tissues (12,24,25). In addition NPr polysialic acid conjugates have been successfully used as experimental human vaccines against group B meningococcal in a number of animal species without deleterious consequences (15,26).…”

Sequences at the Interface of the Fifth Immunoglobulin Domain and First Fibronectin Type III Repeat of the Neural Cell Adhesion Molecule Are Critical for Its Polysialylation

“…In mammals, polyST expression decreases soon after birth, and in the adult animal NCAM is mostly unpolysialylated except in a few specific areas of the brain that require on-going cell migration and synaptic plasticity, such as the hippocampus, hypothalamus, and olfactory bulb (13,(17)(18)(19)(20). In addition, polysialic acid is aberrantly expressed in several pediatric and adult cancers, such as neuroblastoma, small and nonsmall cell lung carcinoma, and Wilms' tumor (21)(22)(23)(24)(25)(26). Polysialic acid re-expression in cancer cells has been suggested to increase tumor invasiveness and to promote tumor growth by down-regulating NCAM signaling that activates tumor suppression pathways (27).…”

Possible Intraspinal Metastasis of a Canine Spinal Cord Nephroblastoma

“…In contrast, canine spinal cord nephroblastoma is immunoreactive for antibody to polysialic acid, which is expressed by embryonic kidney cells and the human renal nephroblastoma. 7,9 Recently a gene, the Wilm's tumor gene, has been identified in human nephroblastoma. 6 The Wilms' tumor gene protein product, WT1, has been identified by immunohistochemistry in a canine spinal cord nephroblastoma, further substantiating classifying these neoplasms as renal in origin.…”