INVESTIGADORES
ALONSO Daniel Fernando
artículos
Título:
Exogenous incorporation of neugc-rich mucin augments n-glycolyl sialic acid content and promotes malignant phenotype in mouse tumor cell lines
Autor/es:
MR GABRI; LL OTERO; DE GOMEZ; DF ALONSO
Revista:
JOURNAL OF EXPERIMENTAL AND CLINICAL CANCER RESEARCH
Editorial:
BIOMED CENTRAL LTD
Referencias:
Año: 2009 vol. 28 p. 146 - 146
ISSN:
1756-9966
Resumen:
BACKGROUND:
Carbohydrates embedded in the plasma membrane
are one of the main actors involved in the communication of cells with
the microenvironment. Neuraminic sialic acids are glycocalyx sugars that
play important roles in the modulation of malignant cell behaviour.
N-glycolylneuraminic acid (NeuGc) is synthesized by the cytidine
monophospho-N-acetylneuraminic acid hydroxylase (CMAH), an enzyme
expressed in all mammals except humans. In mice, this sugar is
synthesized in several somatic tissues.
METHODS:
We used
the B16 melanoma and F3II mammary carcinoma mouse tumor cell lines. By
CMAH directed RT-PCR and NeuGc detection with the specific
anti-NeuGc-GM3 antibody 14F7 we evaluated enzyme and ganglioside
expression in tumor cells, respectively. Expression of NeuGc-GM3
ganglioside was reached by in vitro incubation with NeuGc-rich bovine
submaxillary mucin and evaluated by slot-blot and immunohistochemistry
assays using the 14F7 antibody. Tumor cells treated with mucin or
purified NeuGc were injected s.c. and i.v. in syngeneic mice to evaluate
tumor and metastatic growth.
RESULTS:
In the present
work we demonstrated the absence of expression of CMAH enzyme in B16
melanoma and F3II mammary carcinoma cells. In vitro incubation of these
NeuGc-negative cells with NeuGc-rich mucin increased the presence of
NeuGc in cell membranes for at least 48-72 h, as a component of the GM3
ganglioside. Preincubation with NeuGc-rich mucin reduced tumor latency
and increased the metastatic potential of tumor cells in syngeneic
animals. Similar results were obtained when cells were incubated with
purified NeuGc alone.
CONCLUSION:
Our results indicate
that B16 and F3II mouse tumor cell lines do not express NeuGc in cell
membranes but they are able to incorporate NeuGc from an exogenous
source, contributing to the malignant phenotype of melanoma and mammary
carcinoma cells.