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Metastatic properties of distinct phenotypic classes of lectin-resistant mutants isolated from murine MDAY-D2 cell
Abstract:
Single-step mutants were isolated from the murine metastatic MDAY-D2 cell line after selection in toxic concentrations of wheat-germ agglutinin. They were partially characterized by measuring their relative level of resistance to WGA, PHA, Con A, RIC, and LCA (Lec phenotype), and by comparing their karyotype and their ability to produce metastases upon transplantation into syngeneic DBA/2 mice. Based on their Lec phenotype, a total of 19 independent isolates were ranked into 10 distinct classes. Among them, two EMS-induced mutants were nontumorigenic (Lec II, Lec III), one nonmetastatic (Lec IV), and one spontaneous mutant (Lec I) failed to produce blood-borne metastases. Other spontaneous mutants belonging to Lec I, Lec II, and other classes were as metastatic as their parents. The Lec IV phenotype was found to segregate independently from metastatic potential in somatic hybrids. Metastatic ability was recovered in mutants expressing the Lec IV phenotype, after further selection for resistance to RIC. Our results strongly suggest that the loss or reduction of the invasive property of tumor cells is associated with only few Lecr1 phenotypes and, therefore, that a restricted number of cell surface glyconjugates are essential for this particular function.
Insights
Researchers identified specific cell surface changes linked to reduced tumor cell invasion. Loss of certain lectin phenotypes correlated with decreased metastatic potential in mouse models, highlighting key molecules in cancer spread.
Area of Science:
- Cancer Biology
- Cell Surface Glycobiology
- Metastasis Research
Background:
- The MDAY-D2 murine cell line is highly metastatic.
- Cell surface glycoconjugates play roles in cell adhesion and invasion.
- Lectin resistance phenotypes can indicate alterations in cell surface carbohydrates.
Purpose of the Study:
- To investigate the relationship between lectin resistance phenotypes and the metastatic potential of tumor cells.
- To identify specific cell surface glycoconjugates essential for tumor cell invasion and metastasis.
Main Methods:
- Isolation and characterization of single-step mutants from the MDAY-D2 cell line.
- Selection for resistance to various lectins (WGA, PHA, Con A, RIC, LCA).
- Assessment of metastatic potential in syngeneic DBA/2 mice and analysis of somatic hybrids.
Main Results:
- 19 independent mutants were classified into 10 distinct lectin (Lec) phenotype classes.
- Nontumorigenic (Lec II, Lec III) and nonmetastatic (Lec IV) mutants were identified.
- The Lec IV phenotype segregated independently from metastatic potential, but metastatic ability was restored upon further selection.
Conclusions:
- A restricted number of cell surface glycoconjugates are essential for tumor cell invasion.
- Loss or reduction of specific lectin phenotypes is associated with decreased metastatic properties.
- Targeting these specific glycoconjugates may offer strategies to inhibit cancer metastasis.