Summary
The intermediate filament cytoskeleton of stromal myofibroblasts from a series of twenty-eight infiltrating ductal breast carcinomas was examined by transmission electron microscopy (TEM) and indirect immunofluorescence (IF), the latter using antibodies to desmin, vimentin and prekeratin. Three cases of fibromatoses, selected as an additional source of myofibroblasts, were processed in the same manner. Stromal myofibroblasts from invasive ductal breast carcinomas rich in actin and readily identified by IF, were most numerous in the “young” edematous mesenchyme, areas corresponding to early stromal invasion or the peripheral invasive cellular front. Within the central sclerotic zone wherein clusters of neoplastic epithelial cells were surrounded by abundant collagen, most stromal cells corresponded by TEM to fibroblasts. In like fashion, myofibroblasts were most numerous in cellular, poorly collagenized portions of fibromatoses. By IF the only detectable intermediate filament protein of myofibroblasts in these two settings was vimentin.
Since the appearance of stromal myofibroblasts appears to be associated with stromal invasion by malignant epithelium, their development by modulation of pre-existent periductal fibroblasts is postulated. With the exception of vascular smooth muscle cells and endothelial cells, the only periductal mesenchymal cells shown to contain vimentin were fibroblasts. The lack of desmin in myofibroblasts constitutes evidence against an origin from vascular smooth muscle cells. Because the molecular markers (intermediate filament proteins) of stromal cell differentiation presented quantitative but not qualitative modifications, the transformation of fibroblasts into myofibroblasts is quite likely, suggesting that myofibroblasts may be more closely related to fibroblasts than to smooth muscle cells.
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References
Ahmed A (1978) Atlas of the ultrastructure of human breast diseases. Churchill Livingstone, Edinburgh, p 88
Bannasch P, Zerban H, Schmid E, Franke WW (1980) Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments. Proc Natl Acad Sci USA 77:4948–4952
Frank ED, Warren L (1981) Aortic smooth muscle cells contain vimentin instead of desmin. Proc Natl Acad Sci USA 78:3020–3024
Franke WW, Schmid E, Osborn M, Weber K (1978) Intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci USA 75:5034–5038
Franke WW, Schmid E, Winter S, Osborn M, Weber K (1979) Widespread occurrence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. Exp Cell Res 123:25–46
Franke WW, Schmid E, Freudenstein C, Appelhans B, Osborn M, Weber K, Keenan T (1980) Intermediate-sized filaments of the prekeratin type in myoepithelial cells. Cell Biol 84:633–654
Franke WW, Schmid E, Schiller DL, Winter S, Jarasch ED, Moll R, Denk H, Jackson BW (1982) Differentiation-related patterns of expression of proteins of intermediate-sized filaments in tissues and cultured cells. Cold Spring Harbor Symp Quant Biol 46:431–453
Gabbiani G, Ryan GB, Majno G (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27:549–550
Gabbiani G, Hirschel BJ, Ryan GB, Statkov PR, Majno G (1972) Granulation tissue as a contractile organ. A study of structure and function. J Exp Med 135:719–734
Gabbiani G, Le Lous M, Bailey AJ, Bazin S, Delauney A (1976) Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunological study. Virchows Arch [Cell Pathol] 21:133–145
Gabbiani G, Schmid E, Winter S, Chaponnier C, de Chastonay C, Vandekerckhove J, Weber K, Franke WW (1981) Vascular smooth muscle cells: Predominance of vimentin and specific-type actin. Proc Natl Acad Sci USA 78:298–302
Gabbiani G, Rungger-Brändle E, de Chastonay C, Franke WW (1982) Vimentin containing smooth muscle cells in aortic intimal thickening after endothelial injury. Lab Invest 47:265–269
Gabbiani G, Kapanci Y, Barazzone P, Franke WW (1981) Immunohistochemical identification of intermediate-sized filaments in human neoplastic cells: a diagnostic aid to the surgical pathologist. Am J Pathol 104:206–216
Geisler N, Weber K (1980) Purification of smooth muscle desmin and a protein-chemical comparison of desmins from chicken gizzard and dog stomach. Eur J Biochem 111:425–433
Hirschel BJ, Gabbiani G, Ryan GB, Majno G (1971) Fibroblasts of granulation tissue: immunofluorescent staining with antismooth muscle serum. Proc Soc Exp Biol Med 138:466–469
Hubbard BD, Lazarides E (1979) Copurification of actin and desmin from chicken smooth muscle and their copolymerization in vitro to intermediate filaments. J Cell Biol 80:166–182
Kahn HJ, Yeger H, Baumal R, Heather T, Phillips MJ (1983) Categorization of pediatric neoplasms by immunostaining with anti-prekeratin and anti-vimentin antisera. Cancer 51:645–653
Kahn HJ, Wedad H, Yeger H, Baumal R (1982) Immunohistochemical localization of prekeratin filaments in benign and malignant cells in effusions. Am J Pathol 109:206–214
Lagacé R, Schürch W, Seemayer TA (1980) Myofibroblasts in soft tissue sarcomas. Virchows Arch [Pathol Anat] 389:1–11
Lazarides E (1975) Immunofluorescence studies on the structure of actin filaments in tissue culture cells. J Histochem Cytochem 23:507–528
Lazarides E (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283:249–256
Majno G, Gabbiani G, Hirschel BJ, Statkov PR (1971) Contraction of granulation tissue in vitro: similarity to smooth muscle. Science 173:548–550
Nagle RB, McDaniel KM, Clark VA, Parjne CM (1983) The use of antikeratin antibodies in the diagnosis of human neoplasms. Am J Clin Pathol 79:458–466
Osborn M, Weber K (1983) Biology of diseases. Tumor diagnosis by intermediate filament typing: a novel tool for surgical pathology. Lab Invest 48:372–394
Ozzello L (1971) Ultrastructure of the human mammary gland. Pathol Ann 6:1–60
Schmid E, Osborn M, Rungger-Brändle E, Gabbiani G, Weber K, Franke WW (1982) Distribution of vimentin and desmin filaments in smooth muscle tissue of mammalian and avian aorta. Exp Cell Res 137:329–340
Schürch W, Seemayer TA, Lagacé R (1981) Stromal myofibroblasts in primary invasive and metastatic carcinomas. A combined immunological, light and electron microscopy study. Virchows Arch [Pathol Anat] 391:125–139
Schürch W, Lagacé R, Seemayer TA (1982) Myofibroblastic stromal reaction in retracted scirrhous carcinomas of the breast. Surgery Gynecol Obstet 154:351–358
Seemayer TA, Schürch W, Lagacé R, Tremblay G (1979) Myofibroblasts in the stroma of invasive and metastatic carcinoma. Am J Surg Pathol 3:525–533
Seemayer TA, Lagacé R, Schürch W, Thelmo WC (1980) The myofibroblast: Biological, pathological and theoretical considerations. Pathol Ann 15:443–470
Seemayer TA, Schürch W, Lagacé R (1981) Myofibroblasts in human pathology. Hum Pathol 12:491–492
Sun TT, Green H (1978) Immunofluorescent staining of keratin fibers in cultured cells. Cell 14:469–476
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Schürch, W., Seemayer, T.A., Lagacé, R. et al. The intermediate filament cytoskeleton of myofibroblasts: An immunofluorescence and ultrastructural study. Vichows Archiv A Pathol Anat 403, 323–336 (1984). https://doi.org/10.1007/BF00737283
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DOI: https://doi.org/10.1007/BF00737283