Expression of different tenascin isoforms in normal, hyperplastic and neoplastic human breast tissues

Borsi, Laura; Bárbara, Cristina; Nicoló, Guido; Spina, Bruno; Tanara, G.; Zardi, Luciano

doi:10.1002/ijc.2910520504

Cited by 158 publications

(118 citation statements)

References 25 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…Results of our immunoblotting generally paralleled those in a previous report comparing two other monoclonal antibodies. 8 Analysis by immunoblotting with BC-7 showed two bands of Tn-C at 330 kd and 190 kd in extract from breast cancer tissues, but only the lower band in the normal and benign tissues. When BC-2 against FNIII A was used, only the higher band was labeled in cancer tissue extracts.…”

Section: Discussionmentioning

confidence: 94%

“…[17][18][19][20][21] The size of Tn-C monomers varies as a result of alternative splicing in the FN III repeats at the pre-mRNA level. There are eight conserved FN III repeats (designated as numbers [1][2][3][4][5][6][7][8] and, in the case of human Tn-C, up to nine alternatively spliced FN III repeats (designated as letters A-D) inserted between the conserved repeats 5 and 6. In adults, the smallest Tn-C variant in which the alternatively spliced domain is spliced out is present in static tissues such as cartilage, 22 whereas large variants containing the alternatively spliced FNIII domains in various combinations are found in developing tissues [23][24][25] and in pathological tissues which undergo remodeling, as with regeneration, inflammation, and tumorigenesis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Tsunoda

Inada

Kalembeyi

et al. 2003

The American Journal of Pathology

104

View full text Add to dashboard Cite

Alternative splicing of fibronectin-like type III (FNIII) repeats of tenascin-C (Tn-C) generates a number of splice variants. The distribution of large variants, typical components of provisional extracellular matrices that are up-regulated during tumor stroma remodeling, was here studied by immunoblotting and immunohistochemistry using a monoclonal antibody against the FNIII B domain (named 4C8MS) in a series of human breast cancers. Large Tn-C variants were found at only low levels in normal breast tissues, but were highly expressed at invading sites of intraductal cancers and in the stroma of invasive ductal cancers, especially at invasion fronts. There was a positive correlation between the expression of large Tn-C variants and the cell proliferation rate determined by immunolabeling of the Ki-67 antigen. Of the Tn-C recombinant fragments (all FNIII repeats or mFNIII FL, the conserved FNIII domain only, the epidermal growth factor-like domain, and the fibrinogen-like domain) which were expressed by CHO-K1 cells transfected with mouse Tn-C cDNAs, only the mFNIII FL enhanced in vitro migration and mitotic activity of mammary cancer cells derived from a Tn-C-null mouse. Addition of 4C8MS blocked the function of mFNIII FL. These findings provide strong evidence that the FNIII alternatively spliced region has important roles in tumor progression of breast cancer. During tumor progression, the cancer stroma becomes remodeled by both tumor cells and stromal cells, and protein components of the extracellular matrix (ECM) are dynamically changed by degradation and neosynthesis. Cellular interaction with the ECM strongly influences the behavior of cancer and stromal cells, resulting in modulation of cell growth, migration, differentiation, and apoptosis. 1-3 Compositional change of the ECM in cancer stroma is thus a key determinant of tumor growth and cancer progression. A variety of ECM glycoproteins, such as tenascin-C (Tn-C) and fibronectin, are overexpressed in cancer stroma. In addition, splice variants of these proteins, which are generally absent in normal adult tissues, become predominant. 4 -11 It has been reported that overexpression of Tn-C in breast cancer is related to a poor prognosis, and local and distant recurrence, 12-14 this being attributable to the ability to promote cell migration and proliferation demonstrated in vitro. 15,16 Tn-C is a hexameric glycoprotein, each subunit consisting of a TA (Tn assembly) domain; 14 ϩ 1/2 epidermal growth factor (EGF)-like domains, a variable number of fibronectin type III (FN III) repeats, and a C-terminal fibrinogen-related domain (FBG). [17][18][19][20][21] The size of Tn-C monomers varies as a result of alternative splicing in the FN III repeats at the pre-mRNA level. There are eight conserved FN III repeats (designated as numbers 1-8) and, in the case of human Tn-C, up to nine alternatively spliced FN III repeats (designated as letters A-D) inserted between the conserved repeats 5 and 6. In adults, the smallest Tn-C variant in which the alternatively splic...

show abstract

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Tsunoda

Inada

Kalembeyi

et al. 2003

The American Journal of Pathology

104

View full text Add to dashboard Cite

show abstract

“…Expression of the Str1 transgene during pregnancy and lactation also led to enhanced expression of endogenous Str1 by mammary ®broblasts, collagen accumulation (®brosis), neovascularization, and tenascin-C expression (Thomasset et al, 1998). These changes are not only hallmarks of the reactive stroma seen during involution, but are also seen during cancer progression (Borsi et al, 1992;Rùnnov-Jessen et al, 1996) and may even predispose toward neoplastic epithelial transformation (Jacobs et al, 1999;Jacoby et al, 1997;Kinzler and Vogelstein, 1998;Willenbucher et al, 1999). Furthermore, the proliferative e ects of Str1 could support neoplastic transformation and its apoptotic e ects could help select apoptosis-resistant clones.…”

Section: Introductionmentioning

confidence: 99%

The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter

2000

View full text Add to dashboard Cite

Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably upregulated in epithelial cancers and are key agonists in angiogenesis, invasion and metastasis. Yet most MMPs are secreted not by the cancer cells themselves, but by stromal cells within and around the tumor mass. Because the stromal environment can in¯uence tumor formation, and because MMPs can alter this environment, MMPs may also contribute to the initial stages of cancer development. Several recent studies in MMP-overexpressing and MMP-de®cient mice support this possibility, but have required carcinogens or pre-existing oncogenic mutations to initiate tumorigenesis. Here we review the spontaneous development of premalignant and malignant lesions in the mammary glands of transgenic mice that express an autoactivating form of MMP-3/stromelysin-1 under the control of the whey acidic protein gene promoter. These changes were absent in nontransgenic littermates and were quenched by co-expression of a human tissue inhibitor of metalloproteinases-1 (TIMP-1) transgene. Thus by altering the cellular microenvironment, stromelysin-1 can act as a natural tumor promoter and enhance cancer susceptibility.

show abstract

“…In cultured human cell lines, eight different mRNA species, containing varying numbers of fibronectin type III repeats, have been identified (Siri et al, 1991;Sriramarao and Bourdon, 1993). The larger isoforms of TN are often associated with rapidly proliferating and migrating cells (Borsi et al, 1992).…”

mentioning

confidence: 99%

Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours

Wilson

Langdon²,

Lessells³

et al. 1996

Br J Cancer

View full text Add to dashboard Cite

Summary The extracellular matrix protein tenascin (TN) is overexpressed in a number of solid tumours. This, however, is the first study to examine TN expression in ovarian tumours. TN protein was examined in frozen sections of 50 human ovarian tumours by immunohistochemistry. Malignant and borderline tumours showed a significantly greater incidence and intensity of stromal staining than benign tumours (P<0.0001 and P=0.038 respectively). Seven omental metastases were also examined and showed a strikingly similar protein distribution to their primary tumour counterparts. The expression pattern of different RNA isoforms, created by alternative splicing of the primary transcript, was identified using reverse transcription-polymerase chain reactions (RT-PCR). The smallest TN RNA splice variant (284 bp) was found in all tumours examined, while the appearance of larger molecular weight transcripts (-490 and 556 bp), as major forms, was predominantly limited to malignant tumours, with 9/12 malignant tumours showing this pattern compared with 1/6 benign tumours. These data suggest that malignant ovarian tumours have increased expression of TN compared with benign tumours and this may be associated with induction of specific isoforms.

show abstract

Expression of different tenascin isoforms in normal, hyperplastic and neoplastic human breast tissues

Cited by 158 publications

References 25 publications

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter

Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours

Contact Info

Product

Resources

About