# SIALYLATION OF A TUMOR CELL GLYCOPROTEIN

> **NIH NIH R01** · UNIVERSITY OF MAINE · 1988 · $76,181

## Abstract

Two very different kinds of observations suggest that sialic acid may play
a role in the mechanism of or be indicative of human cancer.  First, sialic
acid-rich mucins have been shown to mask cell-surface antigens and
increased metastasis and resistance to natural killer (NK) cell-mediated
lysis have been correlated with increased sialic acid content.  Second, a
specific sialic acid derivative, N-glycolylneuraminic acid (NeuGl), is not
a constituent of normal human tissue, but has been associated with tissues
or sera from patients with lymphoma, leukemia, neuroblastoma, and colon
cancer.  The proposed work will address two questions:  1) What is the
relationship between susceptibility to NK-mediated cytolysis and expression
of sialic-acid rich mucin?  2) How is the synthesis and incorporation of
NeuGl regulated?  Rat mammary tumor ascites cell (13762 MAT-Bl and MAT-Cl)
will be used as the system of study, because greater than 80% of the sialic
acid in both lines is associated with a major mucin-type glycoprotein.
Expression of this glycoprotein can be reversibly inhibited upon culturing
in vitro.  Also, the MAT-Bl and MAT-Cl glycoproteins differ in the presence
of NeuGl.  The relationship of NK susceptibility and expression of mucin
will be determined by monitoring, as a function of time in culture, a)
glycoprotein production by glucosamine labeling and density gradient
centrifugation, b) NK-susceptibility to normal rat spleen cells, c)
expression of histocompatibility complex by determination of the adsorptive
capacity for rat anti-MHC; d) furthermore, the mechanism for resistance of
ascites cells to NK-mediated cytolysis will be determined.  Regarding the
mechanism of NeuGl formation, the proposed work will e) generate a new and
improved method for assaying the monooxygenase, f) identify the preferred
substrate, requirements and subcellular localization of the enzyme in the
ascites cells, and g) determine whether exogenous N-glycolylmannosamine can
be incorporated into NeuGl in cells where NeuGl is not normally
synthesized.  The results will establish whether cell surface mucins
contribute to resistance to NK-mediated cytolysis in this system, and
provide information on the mechanisms by which levels of sialic acid
derivatives are regulated.  Ultimately through alteration of sialic acid
metabolism, increased recognition and destruction of tumor cells may be
accomplished.

## Key facts

- **NIH application ID:** 3171194
- **Project number:** 5R01CA033238-06
- **Recipient organization:** UNIVERSITY OF MAINE
- **Principal Investigator:** ANNE P CLARK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $76,181
- **Award type:** 5
- **Project period:** 1983-02-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171194

## Citation

> US National Institutes of Health, RePORTER application 3171194, SIALYLATION OF A TUMOR CELL GLYCOPROTEIN (5R01CA033238-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171194. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*