Summary
Tumour basement membrane (BM) is an extracellular matrix produced by tumour cells of epithelial origin. We examined the structure and function of the tumour BM of tumour tissues formed by Lewis lung carcinoma-derived cloned cell lines (P29, LM12-3 and LM60-D6 cells) with low, medium and high metastatic potentials, respectively. Immunohistochemical staining of major BM constituents laminin and type IV collagen demonstrated that all the cell lines produced and deposited these materials extracellularly in vivo. However, the continuity of the tumour BM composed of these materials was much greater in the higher metastatic LM12-3 and LM60-D6 tumours than in those with the low metastatic P29 tumour. Electron microscopic examination revealed that in the higher metastatic tumours, especially the LM60-D6 tumour, the tumour BM had a highly organized structure consisting of lamina densa and lamina rara. Parallel bilayers of BM and their fusion were often observed and tumour cells were in direct contact with the BM. In the vicinity of tumour blood vessels, similar interactions between the tumour bM and the vascular BM were observed, and the tumour cells rested on their own BM, the fused BM or the vascular BM. In contrast, in the low metastatic tumour in which the tumour BM was not clearly defined, this close contact between tumour cells and the vascular BM was not observed. In vitro studies showed that the higher metastatic cells adhered more firmly than the LMP cells to a subendothelial matrix. These results suggest that the adhesiveness of tumour cells to the vascular BM in vivo is correlated with their ability to form an integrated BM in vivo, and that this adhesiveness of the tumour cells may be mediated in part by the tumour BM via BM fusion.
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References
Abrahamson DR (1985) Origin of the glomerular basement membrane visualized after in vivo labeling of laminin in newborn rat kidneys. J Cell Biol 100:1988–2000
Banerjee SD, Cohn RH, Bernfield MR (1977) Basal lamina of embryonic salivary epithelia: production by the epithelium and role in maintaining lobular morphology. J Cell Biol 73:445–463
Barsky SH, Siegal GP, Jannotta F, Liotta, LA (1983) Loss of basement membrane components by invasive tumors but not by their benign counterparts. Lab Invest 49: 140–147
Brodt P, Feldman M, Segal B (1983) Differences in the metastatic potential of two sublines of tumour 3LL selected for resistance to natural NK-like effector cells. Cancer Immunol Immunother 16:109–113
Burtin P, Chavanel G, Foidart JM, Martin E (1982) Antigens of basement membrane and peritumoral stroma in human colonic adenocarcinomas: an immunofluorescence study. Int J Cancer 30:13–20
Carter RL, Burman JF, Barr L, Gusterson BA (1985) Immunohistochemical localization of basement membrane type IV collagen in invasive and metastatic squamous carcinomas of the head and neck. J Pathol 147:159–164
Forster SJ, Talbot IC, Critchley DR (1984) Laminin and fibronectin in rectal adenocarcinoma. Relationship to tumour grade, stage and metastasis. Br J Cancer 50: 51–60
Frei JV (1978) Objective measurement of basement membrane abnormalities in human neoplasms of colorectum and of breast. Histopathology 2:107–115
Garcia-Sanz M, Simon-Marin R, Hilario E (1989) Morphological characterization of Lewis lung carcinoma (3LL). A light and electron microscopic study. Tumori 75:23–27
Gould VE, Miller J, Jao W (1975) Ultrastructure of medullary, intraductal, tubular and adenocystic breast carcinomas. Comparative patterns of myoepithelial differentiation and basal lamina deposition. Am J Pathol 78:401–416
Grigioni WF, Biagini G, Garbisa S, D'errico A, Milani M, Mastrorilli M, Vasi V, Villanacci V, Gossetti G, Mancini AM (1987) Immunohistochemical study of basement membrane antigens in bronchioloalveolar carcinoma. Am J Pathol 128:217–224
Grobstein C (1967) Mechanisms of organogenetic tissue interaction. NCI Monogr 26:270–299
Gusterson BA, Warburton MJ, Mitchell D, Kraft N, Hancock WW (1984) Invading squamous cell carcinoma can retain a basal lamina. An immunohistochemical study using a monoclonal antibody to type IV collagen. Lab Invest 51:82–87
Havenith MG, Arends JW, Simon R, Volovics A, Wiggers T, Bosma FT (1988) Type IV collagen immunoreactivity in colorectal cancer. Prognostic value of basement membrane deposition. Cancer 62:2207–2211
Ingber BE, Madri JA, Jamieson JD (1985) Neoplastic disorganization of pancreatic epithelial cell-cell relations. Role of basement membrane. Am J Pathol 121:248–260
Kramer RH, Gonzales R, Nicolson GL (1980) Metastatic tumor cells adhere preferentially to the extracellular matrix underlying vascular endothelial cells. Int J Cancer 26: 639–645
Lamesweerde DL, Henry N, Vaes G (1983) Metastatic heterogeneity of cells from Lewis lung carcinoma. Cancer Res 43: 5314–5320
Liotta LA, Tryggvason K, Garbisa S, Hart I, Folts CM, Shafie S (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284:67–68
Liotta LA, Bao CN, Barsky SH (1983) Tumor invasion and the extracellular matrix. Lab Invest 49:636–649
Murray JC, Liotta LA, Rennard SI, Martin GR (1980) Adhesion characteristics of murine metastatic and nonmetastatic tumour cells in vitro. Cancer Res 40:347–351
Nakajima M, Irimura T, DiFerrante D, DiFerrante N, Nicolson GL (1983) Heparan sulfate degradation: relation to tumor invasion and metastatic properties of mouse B16 melanoma sublines. Science 220:611–613
Nakanishi H, Okayama M, Oguri K, Hayashi K, Tateno H, Hosoda S (1991) Close association between tumour cells and vascular basement membrane in gastric cancer with liver metastasis. An immunohistochemical and electron microscopic study with special attention to extracellular matrices. Virchows Arch [A] 418:531–538
Pal K, Kopper L, Lapis L (1983) Increased metastatic capacity of Lewis lung tumor cell by in vivo selection procedure. Invasion Metastasis 3:174–182
Pitelka DR, Hamamoto ST, Taggart BN (1980) Basal lamina and tissue recognition in malignant mammary tumors. Cancer Res 40:1600–1611
Stenback F, Risteli J, Risteli L (1985) Basement membrane laminin and type IV collagen in endometrical adenocarcinoma: Relation to differentiation and treatment. Oncology 42:370–376
Takenaga K (1984) Characterization of low and high metastatic clones isolated from a Lewis lung carcinoma. Jpn J Cancer Res 75:61–71
Takenaga K, Nakamura Y, Sakiyama S (1988) Differential expression of a tropomyosin isoform in low-and high-metastatic Lewis lung carcinoma cells. Mol Cell Biol 8:3934–3937
Vaccaro CA, Brody JS (1981) Structural features of alveolar wall basement membrane in the adult rat lung. J Cell Biol 91:427–437
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Nakanishi, H., Takenaga, K., Oguri, K. et al. Morphological characteristics of tumours formed by Lewis lung carcinoma-derived cloned cell lines with different metastatic potentials: structural differences in their basement membranes formed in vivo. Vichows Archiv A Pathol Anat 420, 163–170 (1992). https://doi.org/10.1007/BF02358808
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DOI: https://doi.org/10.1007/BF02358808