This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Giorgini, S. Articles by Del Bufalo, D. Search for Related Content PubMed PubMed Citation Articles by Giorgini, S. Articles by Del Bufalo, D.

---

Angiogenesis, Metastasis, and the Cellular Microenvironment

Modulation of bcl-xL in Tumor Cells Regulates Angiogenesis through CXCL8 Expression

¹ Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, and ² Pathology Unit, Sant' Andrea Hospital, University "La Sapienza," Rome, Italy; and ³ Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland

Requests for reprints: Donatella Del Bufalo, Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy. Phone: 39-6-52662537; Fax: 39-6-52662592. E-mail: delbufalo{at}ifo.it

In this paper, we investigated whether bcl-xL can be involved in the modulation of the angiogenic phenotype of human tumor cells. Using the ADF human glioblastoma and the M14 melanoma lines, and their derivative bcl-xL–overexpressing clones, we showed that the conditioned medium of bcl-xL transfectants increased in vitro endothelial cell functions, such as proliferation and morphogenesis, and in vivo vessel formation in Matrigel plugs, compared with the conditioned medium of control cells. Moreover, the overexpression of bcl-xL induced an increased expression of the proangiogenic interleukin-8 (CXCL8), both at the protein and mRNA levels, and an enhanced CXCL8 promoter activity. The role of CXCL8 on bcl-xL–induced angiogenesis was validated using CXCL8-neutralizing antibodies, whereas down-regulation of bcl-xL through antisense oligonucleotide or RNA interference strategies confirmed the involvement of bcl-xL on CXCL8 expression. Transient overexpression of bcl-xL led to extend this observation to other tumor cell lines with different origin, such as colon and prostate carcinoma. In conclusion, our results showed that CXCL8 modulation by bcl-xL regulates tumor angiogenesis, and they point to elucidate an additional function of bcl-xL protein. (Mol Cancer Res 2007;5(8):761–71)