Abstract
Interactions of tumor cells with the endothelium and tissue stroma are considered to be critical steps in metastasis formation and progression of cancer. To identify cellular receptors that mediate the binding of tumor cells to endothelium, a murine T cell lymphoma-derived expression library was screened for adhesion-inducing cDNA clones. We identified a novel cell adhesion-promoting molecule, termed ARM-1 (adhesion regulating molecule-1), which is homologous to a human M r 110.000 tumor-associated antigen. The ARM-1 cDNA codes for a type I transmembrane protein of 407 amino acids with potential O- and N-glycosylation sites that does not belong to any of the known families of cell adhesion molecules. Overexpression of ARM-1 in 293T human embryonic kidney cells significantly increased adhesion to different endothelial cells. ARM-1 expression in 293T cells did not alter integrin expression or β1-integrin-mediated cell adhesion. Northern blot analysis of human breast cancer cell lines revealed 3- to 5-fold elevated ARM-1 mRNA levels in metastatic as compared to non-metastatic cells. In conclusion, we have identified ARM-1 as a novel cell adhesion-promoting receptor that is upregulated in metastatic cancer cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ebnet K, Kaldjian EP, Anderson AO et al. Orchestrated information transfer underlying leukocyte endothelial interactions. Annu Rev Immunol 1996; 14: 155–77.
Rossiter H, Alon R, Kupper TS. Selectins, T-cell rolling and inflammation. Mol Med Today 1997; 3: 214–22.
Öbrink B. CEA adhesion molecules: multifunctional proteins with signal-regulatory properties. Curr Opin Cell Biol 1997; 9: 616–26.
Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol 1995; 57: 607–34.
Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1994; 1198: 11–26.
Kincade PW, Zheng Z, Katoh S et al. The importance of cellular environment to function of the CD44 matrix receptor. Curr Opin Cell Biol 1997; 9: 635–42.
Varner JA, Cheresh DA. Integrins and cancer. Curr Opin Cell Biol 1996; 8: 724–30.
Guilford P, Hopkins J, Harraway J et al. E-cadherin germline mutations in familial gastric cancer. Nature 1998; 392: 402–5.
Perl A-K, Wilgenbus P, Dahl U et al. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 1998; 392: 190–3.
Nakamori S, Ota DM, Cleary KR et al. MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology 1994; 106: 353–61.
Ho SB, Niehans GA, Lyftogt C et al. Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res 1993; 53: 641–651.
Hanski C, Drechsler K, Hanisch FG et al. Altered glycosylation of the MUC-1 protein core contributes to the colon carcinoma-associated increase of mucin-bound sialyl-Lewis(x) expression. Cancer Res 1993; 53: 4082–8.
Zutter MM, Santoro SA. The ups and downs of α2β1-integrin expression: contributions to epithelial cell differentiation and the malignant phenotype. Cancer Res 1998; 167–85.
Zutter MM, Santoro SA, Staatz WD et al. Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc Natl Acad Sci USA 1995; 92: 7411–5.
Zutter MM, Krigman HR, Santoro SA. Altered integrin expression in adenocarcinoma of the breast. Analysis by in situ hybridization. Am J Pathol 1993; 142: 1439–48.
Qian F, Vaux DL, Weissman IL. Expression of the integrin α4β1 on melanoma cells can inhibit the invasive stage of metastasis formation. Cell 1994; 77: 335–47.
Holzmann B, Gosslar U, Bittner M. α4-Integrins and tumor metastasis. Curr Topics Microbiol Immunol 1998; 231: 125–41.
Gosslar U, Jonas P, Luz A et al. Predominant role of α4-integrins for distinct steps of lymphoma metastasis. Proc Natl Acad Sci USA 1996; 93: 4821–6.
Zahalka MA, Naor D. β2-Integrin dependent aggregate formation between LB T cell lymphoma and spleen cells: Assessment of correlation with spleen invasiveness. Int Immunol 1994; 6: 917–24.
Zahalka MA, Okon E, Naor D. Blocking lymphoma invasiveness with a monoclonal antibody directed against the β-chain of the leukocyte adhesion molecule (CD18). J Immunol 1993; 150: 4466–77.
Lugasi H, Hajos S, Murphy JR et al. Murine spontaneous T-cell leukemia constitutively expressing IL-2 receptor-a model for human T-cell malignancies expressing IL-2 receptor. Int J Cancer 1990; 45: 163–7.
Harder R, Uhlig H, Kashan A et al. Dissection of murine lymphocyteendothelial cell interaction mechanisms by SV-40-transformed mouse endothelial cell lines: Novel mechanisms mediating basal binding, and α4-integrin-dependent cytokine-induced adhesion. Exp Cell Res 1991; 197: 259–67.
Schiemann S, Schwirzke M, Brunner N et al. Molecular analysis of two mammary carcinoma cell lines at the transcriptional level as a model system for progression of breast cancer. Clin Exp Metastasis 1998; 16: 129–39.
Schwirzke M, Gnirke A, Bork P et al. Differential gene expression in mammary carcinoma cell lines: Identification of DRIM, a new gene down-regulated in metastasis. Anticancer Res 1998; 18: 1409–21.
Fairchild CR, Ivy SP, Kao-Shan C-S et al. Isolation of amplified and overexpressed DNA sequences from adriamycinresistant human breast cancer cells. Cancer Res 1987; 47: 5141–8.
Brinkley BR, Beall PT, Wible LJ et al. Variations in cell form and cytoskeleton in human breast carcinoma cells in vitro. Cancer Res 1980; 40: 3118–29.
Rietzler M, Bittner M, Kolanus W et al. The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of β7-integrins. J Biol Chem 1998; 273: 27459–66.
Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 1987; 7: 2745–50.
Altschul SF, Madden TL, Schäffer AA et al. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res 1997; 25: 3389–402.
Chirgwin JM, Przybyla AE, MacDonald RJ et al. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 1979; 18: 5294–9.
Naor D, Sionov RV, Zahalka M et al. Organ-specific requirements for cell adhesion molecules during lymphoma cell dissemination. Curr Topics Microbiol Immunol 1998; 231: 143–66.
Zahalka MA, Okon E, Gosslar U et al. Lymph node (but not spleen) invasion by murine lymphoma is both CD44-and hyaluronatedependent. J Immunol 1995; 154: 5345–55.
Nielsen H, Engelbrecht J, Brunak S et al. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Engineering 1997; 10: 1–6.
Hansen JE, Lund O, Rapacki K et al. O-glycbase version 2.0 – a revised database of O-glycosylated proteins. Nucleic Acids Res 1997; 25: 278–82.
Hansen JE, Lund O, Tolstrup N et al. NetOglyc: Prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility. Glycoconjugate J 1998; 15: 115–30.
Shimada S, Ogawa M, Schlom J et al. Identification of a novel tumorassociated M r 110,000 gene product in human gastric carcinoma cells that is immunologically related to carcinoembryonic antigen. Cancer Res 1991; 51: 5694–703.
Shimada S, Ogawa M, Takahashi M et al. Molecular cloning and characterization of the complementary DNA of an M r 110,000 antigen expressed by human gastric cells and upregulated by γ-inteferon. Cancer Res 1994; 54: 3831–6.
Sutherlin ME, Nishimori I, Caffrey T et al. Expression of three UDP-N-acetyl-α-D-galactosamine:polypeptide GalNAc N-acetylagalactosaminyltransferases in adenocarcinoma cell lines. Cancer Res 1997; 57: 4744–8.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Simins, A.B., Weighardt, H., Weidner, K.M. et al. Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells. Clin Exp Metastasis 17, 641–648 (1999). https://doi.org/10.1023/A:1006790912877
Issue Date:
DOI: https://doi.org/10.1023/A:1006790912877