The use of the lectin Helixpomatia agglutinin (HPA) as a prognostic indicator and as a tool in cancer research

Abstract

Progress in treatment for cancer has enabled extension of the disease-free interval, and of the quality of life for patients, but there has been very little improvement in overall survival rates. The main reason for this has been the ineffectiveness of current therapies to kill all the cancer cells once they have spread to distant sites to form metastatic deposits. One marker which has proved to be useful in identifying those cancers which have the potential to spread is the lectin Helixpomatia agglutinin (HPA). In clinical studies, HPA binding to primary tumours in tissue sections has been of prognostic value in breast, colon and gastric cancer, while no prognostic significance for HPA could be detected in tumours of the head and neck. These studies hence indicate that HPA is best suited to recognise a glycotope on adenocarcinomas. In several studies, HPA reactivity is equal or superior to other classical markers of metastatic potential. Since HPA is a marker of prognosis at the level of individual tumour cells, human tumour cell lines were screened for their HPA positivity. When transplanted into severe combined immunodeficient (scid) mice, HPA positive human breast and colon cancer cells metastasised while HPA negative cancer cell lines in general did not. In order to define HPA binding glycotopes at the molecular level, isolated cell membrane glycoproteins were exposed to labelled HPA on nitrocellulose membranes after Western blotting procedure. The majority of the isolated cell membrane glycoproteins bound HPA indicating that not a single HPA binding glycoprotein exists, which is associated with the metastatic phenotype. Functional investigations using the humanlscid mouse chimeras will aid in the identification of those HPA positive glycoproteins which are functionally involved in the metastatic cascade.