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  RESEARCH ACTIVITY > Department of Experimental Oncology and Clinical Applications  
Department of Experimental Oncology and Clinical Applications
Research Group
Ida Pucci-Minafra Principal Investigator
Salvatore Minafra Principal Investigator
Gianluca Di Cara PhD Student
Nadia Albanese PhD Student

University of Palermo
Department of Experimental Oncology and Clinical Applications (DOSAC) and Center of Experimental Oncobiology (COBS)
via san Lorenzo Colli, 312 - Palermo Italy

Background and specific aims
Revisitation of the “soil and seed” theory
By the end of last century the English surgeon Stephen Paget published in Lancet the results of a random analysis on 735 histories of fatal breast cancer cases, showing that metastases formed more often in the liver than in any other organ. He made the prophetic hypothesis of the ‘soil and seed’ of metastasis, considered foolish at that time, but becoming of extraordinary actuality in recent years. The current focusing on the “soil”, that is the extracellular microenvironment, begins around years 1980 with publications by I. J. Fidler, A. van den Hoof, G.L. Niolson, L. Liotta, M. J. Bissell, E.D. Hay, S. L. Schor & A. M. Schor, and other outstanding Researchers.
In 1985-6 our research group produced the first evidence that the stroma of the mammary gland undergoes substantial modifications in cases of ductal infiltrating carcinomas (DIC) (Pucci-Minafra et al. 1985, Cell Biol Int Rep, 9(3): 291-296; Anal. Biochem. 1986, 155 (2): 352-357; J Subm. Cytol. 1986, 18(4):795-805). The changes in the collagen framework are caused by both enzymatic degradation (Pucci-Minafra et al. 1987, Int. J. Cancer 39 (5): 599-603) and by defects in the new matrix deposition. Defects include increased collagen synthesis, as compared with healthy tissue (Kauppila et al. 1998, J. Pathol., 186 (3): 262-268), the reappearance of an onco-fetal type I-trimer collagen and increased amount of type V collagen (Pucci-Minafra et al. 1993, Biochemistry 32 (29):7421-7427; Pucci-Minafra et al. 1995, Bioch. Bioph. Res. 207,852-859). The enhanced synthesis is associated with the formation of aberrant collagen bundles, which may be more readily degradable, but also may facilitate breast tumour migration and invasion (Pucci-Minafra et al., 1998, Carcinogenesis, 19 (4): 575-584).
Interestingly, it has been demonstrated that gene expression for neomatrix interstitial collagens occurs before invasion in breast carcinoma is evident (Wapniret al. 1996. Invasion and Metastasis.16 (6): 308-316).
To investigate the biological effects of different collagen types, which likely enter in contact with neoplastic cells during the invasive growth, we utilised an “in vitro” model of cells isolated from a DIC (Minafra et al.1989, Br J Cancer 60 (2):185-192) and cultured on reconstituted collagen substrata. These pionieristic studies showed how strong may be the influence exerted by different collagen types on cytoskeleton organization, cell spreading pattern and motility of breast carcinoma cells (Pucci-Minafra et al.1991, J Subm. Cytol. Pathol 23 (1): 67-74; Luparello et al. 1991, J Cell Sc. 100:179-185). Recently, the study of cellular effects on breast cancer phenotype has been extended to other microenvironmental factors, among which decorin, fibroblastic and endothelial factors, and hypoxia. The cellular responses are being evaluated at proteomic and genomic level.
Figures below show some representative results.
Research projects
Three main areas of interest are presently focused by the group:
• proteomic responses to microenvironment factors underlying breast cancer cell invasion and metastasis;
• clinical applications of proteomics for biomarker search and pathways identification;
• in vitro and in vivo studies of proteolytic enzymes of extracellular matrix.
Facilities and equipment
Fully equipped cell cultures laboratory; fully equipped laboratory for proteomics and protein sequencing (Procise and Maldi-Toff); PCR and Real Time PCR; Microarray Genomics Platform.
Figure 1: A) Electron micrograph of collagen bundles in normal intestinal mucosa B) Electron micrograph of a section of colon carcinoma stroma C) Neoplastic cells (8701-BC) spreading on collagen substrate. F-actins were detected by rhodamine-phalloidin staining and nuclei visualized by DAPI staining. D) Analysis window of a proteomic map of 8701-BC cells, utilised for comparative proteomics of cells grown on different substrates.

Recent pubblications
Breast cancer cells exhibit selective modulation induced by different collagen substrates - Pucci-Minafra I, Albanese NN, Di Cara G, Minafra l, Marabeti MM, Cancemi P - Connect Tissue Res. in press ( 2008 )
New protein clustering of breast cancer tissue proteomics using actin content as a cellularity indicator. - Pucci-Minafra I, Cancemi P, Albanese NN, Di Cara G, Marabeti MR, Marrazzo A, Minafra S. - J Proteome Res. Apr;7(4):1412-8. ( 2008 )
Endothelial cells and normal breast epithelial cells enhance invasion of breast carcinoma cells by CXCR-4-dependent up-regulation of urokinase-type plasminogen activator receptor (uPAR, CD87) expression. - Serratì S, Margheri F, Fibbi G, Di Cara G, Minafra L, Pucci-Minafra I, Liotta F, Annunziato F, Pucci M, Del Rosso M. - J Pathol. Apr;214(5):545-54. ( 2008 )
Decorin transfection induces proteomic and phenotypic modulation in breast cancer cells 8701-BC. - Pucci-Minafra I, Cancemi P, Di Cara G, Minafra L, Feo S, Forlino A, Tira ME, Tenni R, Martini D, Ruggeri A, Minafra S. - Connect Tissue Res. 49(1):30-41. ( 2008 )
Proteomic profiling of 13 paired ductal infiltrating breast carcinomas and non-tumoral adjacent counterparts. - Pucci-Minafra I., Cancemi P, Marabeti M. R, Albanese N. N, Di Cara G, Taormina P, Marrazzo A. - Proteomics Clinical Applications. Vol. 1, 118-129. ( 2007 )
Expanding the protein catalogue in the proteome reference map of human breast cancer cells. - Pucci-Minafra I., Cancemi P, Fontana S, Minafra L, Feo S, Becchi M, Freyria A.M, Minafra S. - Proteomics. 6, 2609-2625. ( 2006 )

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