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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Specific upregulation of RHOA and RAC1 in cancer-associated fibroblasts found at primary tumor and lymph node metastatic sites in breast cancer

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Rozenchan, Patricia Bortman [1, 2, 3] ; Pasini, Fatima Solange [1] ; Roela, Rosimeire A. [1] ; Hirata Katayama, Maria Lucia [1] ; Lopes Mundim, Fiorita Gonzales [4] ; Brentani, Helena [5] ; Lyra, Eduardo C. [6] ; Brentani, Maria Mitzi [1]
Total Authors: 8
[1] Univ Sao Paulo, Sch Med, Radiol & Oncol Dept, BR-01246903 Sao Paulo, SP - Brazil
[2] Colsan Blood Bank Beneficent Assoc, Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Sch Med, Dept Gynecol, Sao Paulo, SP - Brazil
[4] Vale Sapucai Univ, Dept Pathol, Pouso Alegre, MG - Brazil
[5] Univ Sao Paulo, Sch Med, Dept Psychiat, BR-01246903 Sao Paulo, SP - Brazil
[6] Brazilian Inst Canc Control, BR-03102002 Sao Paulo, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: TUMOR BIOLOGY; v. 36, n. 12, p. 9589-9597, DEC 2015.
Web of Science Citations: 11

The importance of tumor-stromal cell interactions in breast tumor progression and invasion is well established. Here, an evaluation of differential genomic profiles of carcinoma-associated fibroblasts (CAFs) compared to fibroblasts derived from tissues adjacent to fibroadenomas (NAFs) revealed altered focal adhesion pathways. These data were validated through confocal assays. To verify the possible role of fibroblasts in lymph node invasion, we constructed a tissue microarray consisting of primary breast cancer samples and corresponding lymph node metastasis and compared the expression of adhesion markers RhoA and Rac1 in fibroblasts located at these different locations. Two distinct tissue microarrays were constructed from the stromal component of 43 primary tumors and matched lymph node samples, respectively. Fibroblasts were characterized for their expression of alpha-smooth muscle actin (alpha-SMA) and vimentin. Moreover, we verified the level of these proteins in the stromal compartment from normal adjacent tissue and in non-compromised lymph nodes. Our immunohistochemistry revealed that 59 % of fibroblasts associated with primary tumors and 41 % of the respective metastatic lymph nodes (p = 0.271) displayed positive staining for RhoA. In line with this, 57.1 % of fibroblasts associated with primary tumors presented Rac1-positive staining, and the frequency of co-positivity within the lymph nodes was 42.9 % (p = 0.16). Expression of RhoA and Rac1 was absent in fibroblasts of adjacent normal tissue and in compromised lymph nodes. Based on our findings that no significant changes were observed between primary and metastatic lymph nodes, we suggest that fibroblasts are active participants in the invasion of cancer cells to lymph nodes and support the hypothesis that metastatic tumor cells continue to depend on their microenvironment. (AU)

FAPESP's process: 09/10088-7 - Gene expression profiling of the tumor fibroblasts in breast cancer classified into subtypes by estrogen and progestorone receptors and ERBB-2 status
Grantee:Maria Mitzi Brentani
Support type: Research Projects - Thematic Grants
FAPESP's process: 04/04607-8 - Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma of the breast
Grantee:Maria Mitzi Brentani
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/03090-3 - 105th AACR Annual Meeting 2014
Grantee:Patricia Bortman Rozenchan
Support type: Research Grants - Meeting - Abroad