The immunoglobulin-like cell adhesion molecule hepaCAM induces differentiation of human glioblastoma U373-MG cells.
Subsequent to our identification of a novel immunoglobulin-like cell adhesion molecule hepaCAM, we showed that hepaCAM is frequently lost in diverse human cancers and is capable of modulating cell motility and growth when re-expressed. Very recently, a molecule identical to hepaCAM (designated as GlialCAM) was found highly expressed in glial cells of the brain. Here, we demonstrate that hepaCAM is capable of inducing differentiation of the human glioblastoma U373-MG cells. Expression of hepaCAM resulted in a significant increase in the astrocyte differentiation marker glial fibrillary acid protein (GFAP), indicating that hepaCAM promotes glioblastoma cells to undergo differentiation. To determine the relationship between hepaCAM expression level and cell differentiation, we established two U373-MG cell lines expressing hepaCAM at different levels. The results revealed that high-level hepaCAM triggered a clear increase in GFAP expression as well as morphological changes characteristic of glioblastoma cell differentiation. Furthermore, high expression of hepaCAM significantly accelerated cell adhesion but inhibited cell proliferation and migration. Concomitantly, deregulation of cell cycle regulatory proteins was detected. Expectedly, the differentiation was noticeably less apparent in cells expressing low-level hepaCAM. Taken together, our findings suggest that hepaCAM induces differentiation of the glioblastoma U373-MG cells. The degree of cell differentiation is dependent on the expression level of hepaCAM.
Lee
Lay Hoon
LH
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, Singapore 117597, Singapore.
Moh
Mei Chung
MC
Zhang
Ting
T
Shen
Shali
S
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C487620:HEPACAM protein, human; D011506:Proteins