Fascin, an actin-bundling protein expression in cervical neoplasms

Purpose of investigation: Our objectives were (1) to examine expression of fascin in cervical tissues with chronic inflammation, intraepithelial neoplasms and invasive carcinomas, and (2) to investigate the role of fascin on endothelial migration and angiogenesis in cervical neoplasms.

Methods: In this study we investigated by means of immunohistochemistry fascin expression in 92 cervical biopsy samples representative of chronic inflammation (n=13), squamous intraepithelial lesions (SILs, n = 33) and invasive carcinomas (n = 46).

Results: Various degrees of fascin expression were observed in 94% of the samples of SILs, in 67% of the samples of invasive cervical carcinoma and in 69% of the samples of chronic inflammation. Total epithelial fascin scores of samples were significantly higher in high-grade (H)SILs compared to low-grade (L)SILs, invasive carcinoma and chronic inflammation of the cervix (p < 0.05). Mean microvessel count was 55.00 +/- 5.17 in HSILs, 40.76 +/- 3.57 in LSILs, 37.11 +/- 2.91 in carcinoma and 25.69 +/- 3.98 in chronic inflammation. We found a significantly higher microvessel count in HSILs compared to invasive carcinoma and chronic inflammation (respectively, p = .004, p = .000).

Conclusion: Epithelial fascin expression up-regulated when the malignant tumor cell phenotype had occurred in the cervix. Similarly, microvessel count increased with the beginning of cervical tumorigenesis.

Fascin; Cervical neoplasms; Angiogenesis

[1] Adams J.C., Clelland J.D., Collet G.D.M. et al.: "Cell-matrix adhesions differentially regulate fascin phosphorylation". Mol. Biol. Cell., 1999, 10, 4177.

[2] Cohan C.S., Welnhofer E.A., Zhao L. et al.: "Role of the actin bundling protein fascin in growth cone morphogenesis: localization in filopodia and lamellipodia". Cell. Motil. Cytoskeleton., 2001, 48, 109.

[3] Duh FM., Latif F., Weng Y.: "cDNA cloning and expression of the human homolog of the sea urchin fascin and Drosophila signed genes which actin-bundling protein". DNA. Cell. Biol., 1994, 13, 821.

[4] Ishikawa R., Yamashiro S., Kohama K. et al.: "Regulation of actm binding and actin bundling activities of fascin by caldesmon coupled with tropomyosin". J. Biol. Chem., 1998, 273, 26991.

[5] Puius Y.A., Mahoney N.M., Almo S.C.:'The modular structure of actin regulatory proteins". Curr. Opin. Cell. Biol., 1998, 10, 23.

[6] Carico E., Atlante M., Bucci B. et al.: "E-cadherin and α-catenin expression during tumor progression of cervical carcinoma". Gynecol. Oneal., 2001, 80, 156.

[7] Fujimoto J., Ichigo S., Hirose R. et al.: "Expression of E-cadherm and α- and β- catenin mRNAs in uterine cervical cancers". Tumor. Biol., 1997, 18, 206.

[8] Bristow R.E., Cervical Cancer. In: Scott J.R., Gibbs R.S., Karlan B.Y., Haney A.F. (eds.), Danforth's Obstetrics and Gynecology. 9th ed,. Philadelphia: Lippincott Williams &Wilkins, 2003, 923.

[9] Goncharuk V.N., Ross J.S., Carlson J.A.: "Actin-binding protein fascin expression in skin neoplasia". J. Cutan. Pathol., 2002, 29, 430.

[10] Grothey A., Hashizume R., Ji H. et al.: "C-erbB-2/Her-2 upregulates fascin, an actin-bundling protein associated with cell motility, in human breast cancer cell lines". Oncogene, 2000, 19, 4864.

[11] Guvakova M.A., Boettiger D., Adams J.C.: "Induction of fascin spikes in breast cancer cells by activation of the insulin-like growth factor-I receptor". Int. J. Biochem. Cell. Biol., 2002, 34, 685.

[12] Jawhari A.U., Buda A., Jenkins M. et al.: "Fascin, an actm bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro". AJP., 2003, 162, 69.

[13] Pelosi G., Pasini F., Sonzogni A. et al.: "Prognostic implications of neuroendocrine differentiation and hormone production in patients with Stage I non small cell lung carcinoma". Cancer, 2003, 97, 2487.

[14] Pelosi G., Barisella M., Pasini F. et al.: "CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients". Mod. Pathol., 2004, 17, 711.

[15] Hu W., McCrea P.D., Deavers M. et al.: "Increased expression of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors". Clin. Exp. Metastasis, 2000, 18, 83.

[16] Maitra A., Iacobuzio-Donahue C., Rahman A. et al.: "Immunoh1stochemical validation of a novel epithelial and a novel stroma marker of pancreatic ductal adenocarcinoma identified by global express microarrays: sea urchin fascin homolog and heat shock protein 47". Am. J. Clin. Pathol., 2002, 118, 52.

[17] Rong J., Xu L.Y., Cai W.J. et al.: "Expression of fascin l gene in the process of the immortalized esophageal carcinoma carcinogenesis". Ai. Zheng., 2004, 23, 243.

[18] Pinkus G.S., Pinkus J.L., Lanhoff E. et al.: "Fascin, a sensitive new marker for Reed-Sternberg cells of Hodgkin's disease. Evidence for a dendritic or B cell derivation?" Am. J. Pathol., 1997, 150, 543.

[19] Kempf W., Levi E., Kamarashev J. et al.: "FasCin expression in CD30-positive cutaneous lymphoproliferative disorders". J. Cutan. Pathol., 2002, 29, 295.

[20] Wong V., Ching D., McCrea P.D., Firestone G.L: "Glucocorticoid down-regulation of fascin protein expression is required for steroid-induced formation of tight junctions and cell-cell interactions in rat mammary epithelial tumor cells". J. Biol. Chem., 1999, 274, 5443.

[21] Guan Y., Woo P.L., Rubenstein N.M., Firestone G.L.: "Transforming growth factor-a abrogates the glucocorticoid stimulation of tight junction formation and reverses the steroid-induced downregulation of fascin in rat mammary epithelial tumor cells by a Ras-depentent pathway". Exp. Cell. Res., 2002, 273, 1.

[22] Krengel S., Groteliishen F., Bartsch S., Tronnier M.: "Cadhenn expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progression". J Cutan. Pathol., 2004, 31, 1.

[23] Shonukan O.T., Bagayogo L, McCrea P.D., Chao M., Hempstead B.: "Neurotropin-induced melanoma cell migration is mediated through actin-bundling protein fascin". Oncogene, 2003, 22, 3616.

[24] Sandhu M.S., Dunger D.B., Giovannucci E.L.: "Insulin, insulinlike growth factor-I (IGF-1), IGF binding proteins, their biologic interactions, and colorectal cancer". J. Natl. Cancer. Inst., 2002, 94, 972.

[25] Furstenberger G., Senn H.J.: "Insulin-like growth factors and cancer". Lancet. Oneal., 2002, 3, 298.

[26] Keehn C.A., Saeed S., Bickle K. et al.: "Expression of insulin-like growth factor-I receptor in primary cutaneous carcinomas". J. Cutan. Pathol., 2004, 31, 368.

[27] Shimabukaro K., Ichinose S., Koike R. et al.: "Hepatocyte growth factor/scatter factor is implicated in the mode of stromal invasion of uterine squamous cervical cancer". Gynaecol. Oneal., 2001, 8, 205.

[28] Tokumo K., Kodama J., Seki N. et al.: "Different angiogenic pathways in human cervical cancers". Gynaecol. Oneal., 1998, 68, 38.

[29] Obermair A., Bancher-Todesca D., Bilgi S. et al.: "Correlation of vascular endothelial growth factor expression and microvessel count in cervical intraepithelial neoplasia". J. Natl. Cancer. Inst., 1997, 89, 1212.

[30] Ozalp S., Yalcin O.T., Oner U. et al.: "Microvessel count as a factor in preinvasive and invasive cervical lesions". Eur. J. Gynaecol. Oneal., 2003, 24, 425.