Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1999 Mar;90(3):320–325. doi: 10.1111/j.1349-7006.1999.tb00750.x

Expression of Fibronectin Isoforms in Human Breast Tissue: Production of Extra Domain A+/Extra Domain B+ by Cancer Cells and Extra Domain A+ by Stromal Cells

Ei‐ichi Matsumoto 1,2, Toshimichi Yoshida 1, Yoshifumi Kawarada 2, Teruyo Sakakura 1,
PMCID: PMC5926068  PMID: 10359047

Abstract

The expression of fibronectin (FN) isoforms including extra domain A (EDA) and extra domain B (EDB) segments, was investigated in 36 invasive ductal carcinomas and 13 benign tumors of human breast tissues by in situ hybridization using probes specific to alternative splicing sites. Signals for the constant region of FN mRNA in cancer cells were found in 53% of the invasive ductal carcinomas. The EDA+ and EDB+ mRNA signals were found in 47% and 33%, respectively. Stromal cells expressing FN, EDA+ and EDB+ mRNA signals were present in 100%, 69% and 14% of cases, respectively. Expression of FN mRNAs by cancer cells was most frequent in intraductal lesions or large cancer nests, and that by stromal cells was associated with desmoplastic areas. In representative cases, proportions of FN mRNA‐positive cancer cells expressing EDA and EDB segments were 45% and 39%, respectively, signals for both being frequently found in the same cells. EDA+ and EDB+ mRNA were labeled in 25% and 6% of the FN mRNA‐positive stromal cells, a large proportion thus being EDA/EDB FN. In conclusion, the splicing pattern of FN pre‐mRNA is dependent on the cell type and histology of breast cancer tissues. The observed lack of expression in fibroadenomas and other benign conditions suggests a link with tumor progression.

Keywords: Fibronectin, EDA, EDB, Breast cancer

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

REFERENCES

  • 1).Carnemolla , B. , Balza , E. , Siri , A. , Zardi , I. , Nicotra , M. R. , Bigoti , A. and Natali , P. G.A tumor‐associated fibronectin isoform generated by alternative splicing of messenger RNA precursors . J. Cell Biol. , 108 , 1139 – 1148 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2).Ffrenchi‐Constant , C. and Hynes , R. O.Alternative splicing of fibronectin is temporally and spatially regulated in the chicken embryo . Development , 106 , 375 – 388 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 3).Oyama , F. , Murata , Y. , Suganuma , N. , Kimura , T. , Titani , K. and Sekiguchi , K.Patterns of alternative splicing of fibronectin pre‐mRNA in human adult and fetal tissues . Biochemistry , 28 , 1428 – 1434 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 4).Pagani , F. , Zagato , L. , Vergani , C. , Casari , G. , Sidoli , A. and Baralle , F. E.Tissue specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat . J. Cell Biol. , 113 , 1223 – 1229 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5).Lantinen , L. , Vartio , T. and Virtanen , I.Cellular fibronectins are differentially expressed in human fetal and adult kidney . Lab. Invest. , 64 , 492 – 498 ( 1991. ). [PubMed] [Google Scholar]
  • 6).Oyama , F. , Hirohashi , S. , Shimosato , Y. , Titani , K. and Sekiguchi , K.Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre‐messenger RNA at ED‐A, ED‐B, and CS1 regions in human liver tumors . Cancer Res. , 53 , 2005 – 2011 ( 1993. ). [PubMed] [Google Scholar]
  • 7).Natali , P. G. , Nicotra , M. R. , Filippo , F. Di. and Bigotti , A.Expression of fibronectin, fibronectin isoforms and integrin receptors in melanocytic lesions . Br. J. Cancer , 71 , 1243 – 1247 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8).Pujuguet , P. , Hammann , A. , Moutet , M. , Samuel , J. L. , Martin , F. and Martin , M.Expression of fibronectin EDA+ and ED‐B+ isoforms by human and experimental colorectal cancer: contribution of cancer cells and tumor‐associated myofibroblasts . Am. J. Pathol. , 148 , 579 – 592 ( 1996. ). [PMC free article] [PubMed] [Google Scholar]
  • 9).Menzin , A. W. , de Mola , J. R. L. , Bilker , W. B. , Wheeler , J. E. , Rubin , S. C. and Feinberg , R. F.Identification of oncofetal fibronectin in patients with advanced epithelial ovarian cancer . Cancer , 82 , 152 – 158 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 10).Gould , V. E. , Koukoulis , G. K. and Virtanen , I.Extracellular matrix proteins and their receptors in the normal, hyperplastic and neoplastic breast . Cell Differ. Dev. , 32 , 409 – 416 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 11).Koukoulis , G. K. , Howeedy , M. , Korhonen , I. , Virtanen , I. and Gould , V. E.Distribution of tenascin, cellular fibronectins and integrins in the normal, hyperplastic and neoplastic breast . J. Submicrosc. Cytol. Pathol. , 25 , 285 – 295 ( 1993. ). [PubMed] [Google Scholar]
  • 12).Kaczmarek , J. , Castellani , P. , Nicolo , G. , Spina , B. , Allemanni , G. and Zardi , L.Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues . Int. J. Cancer , 58 , 11 – 16 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 13).Ffrenchi‐Constant , C.Alternative splicing of fibronectin‐many different proteins but few different functions . Exp. Cell Res. , 221 , 261 – 271 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 14).Manabe , R. , Oh‐e , N. , Maeda , T. , Fukuda , T. and Sekiguchi , K.Modulation of cell adhesive activity of fibronectin by the alternatively spliced EDA segment . J. Cell Biol. , 139 , 295 – 307 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15).Chen , W. and Culp , L. A.Adhesion to fibronectin's EDb domain induces tyrosine phosphorylation of focal adhesion proteins in Balb/c 3T3 cells . Clin. Exp. Metastasis , 16 , 30 – 42 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 16).Ishihara , A. , Yoshida , T. , Tamaki , H. and Sakakura , T.Tenascin expression in cancer cells and stroma of human breast cancer and its prognostic significance . Clin. Cancer Res. , 1 , 1035 – 1041 ( 1995. ). [PubMed] [Google Scholar]
  • 17).Yoshida , T. , Matsumoto , Ei. , Hanamura , N. , Kalembeyi , I. , Katsuta , K. , Ishihara , A. and Sakakura , T.Co‐expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinomas in the human breast . J. Pathol. , 182 , 421 – 428 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 18).Hanamura , N. , Yoshida , T. , Matsumoto , Ei. , Kawarada , Y. and Sakakura , T.Expression of fibronectin and tenascin‐C mRNA by myofibroblasts, vascular cells and epithelial cells in human colon adenomas and carcinomas . Int. J. Cancer , 73 , 10 – 15 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 19).Castellani , P. , Viale , G. , Dorcaratto , A. , Nicolo , G. , Kaczmarek , J. , Querze , G. and Zardi , L.The fibronectin isoform containing the ED‐B oncofetal domain: a marker of angiogenesis . Int. J. Cancer , 59 , 612 – 618 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 20).Tucker , R. P. , Brunso‐Bechtold , J. K. , Jenrath , D. A. , Khan , N. A. , Poss , P. M. and Sweatt , A. J.Cellular origins of tenascin in the developing nervous system . Perspect. Dev. Neurobiol. , 2 , 89 – 99 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 21).Chung , C. Y. , Murphy‐Ullrich , J. E. and Erickson , H. P.Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin‐C interacting with its cell surface receptor, annexin II . Mol. Biol. Cell , 7 , 883 – 892 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES