Email this page

Print this page

Research Paper

Targeting pericytes with a PDGF-B aptamer in human ovarian carcinoma models

Chunhua Lu, Mian M.K. Shahzad, Myrthala Moreno-Smith, Yvonne Lin, Nicholas B. Jennings, Julie K. Allen, Charles N. Landen, Lingegowda S. Mangala, Guillermo N. Armaiz-Pena, Rosemarie Schmandt, Alpa M. Nick, Rebecca L. Stone, Robert B. Jaffe, Robert L. Coleman and Anil K. Sood

Purpose: On the basis of the known role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR) β in pericyte regulation, highly specific inhibitors of this target are needed.  We tested the efficacy of a highly selective aptamer against  PDGF-B with or without anti-VEGF therapy in ovarian cancer models. Experimental Design: The therapeutic efficacy of targeting endothelial cells (bevacizumab) and/or pericytes (PDGF-aptamer, AX102) was examined using HeyA8 and SKOV3ip1 orthotopic models of ovarian cancer metastasis. Following therapy, tumors were examined for microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and vascular maturation (pericyte coverage). Results: Bevacizumab inhibited tumor growth by 45% and 48% in the HeyA8 and SKOV3ip1 models, respectively.  AX102 had minimal effect on the HeyA8 model, but increased tumor growth in the SKOV3ip1 model. However, bevacizumab plus AX102 was more effective than bevacizumab alone, and resulted in 76 - 88% inhibition of tumor growth in both models.  A longitudinal study in the HeyA8 model using bioluminescence imaging showed that combination of bevacizumab, AX102 and paclitaxel caused tumor reduction by 65% (based on bioluminescence imaging).  In the HeyA8 model, MVD and PCNA counts were significantly reduced in the bevacizumab treatment groups, and pericyte coverage was significantly decreased in the AX102 treatment groups.  In the SKOV3ip1 model, MVD and PCNA was significantly reduced in the bevacizumab treatment group, and even lower in the bevacizumab and AX102 combination treatment group. Conclusions: Dual targeting of endothelial cells and pericytes holds potential as an anti-vascular therapeutic approach in ovarian carcinoma.

Authors

Chunhua Lu

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Mian M.K. Shahzad

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030; Department of Obstetrics and Gynecology, Baylor College of Medicine, 1709 Dryden Road, Houston, TX 77030

Myrthala Moreno-Smith

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Yvonne Lin

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Nicholas B. Jennings

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Julie K. Allen

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Charles N. Landen

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Lingegowda S. Mangala

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Guillermo N. Armaiz-Pena

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Rosemarie Schmandt

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Alpa M. Nick

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Rebecca L. Stone

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Robert B. Jaffe

Center for Reproductive Sciences, University of California, San Francisco, 1450 HSW, San Francisco, CA 94143

Robert L. Coleman

Department of Gynecologic Oncology, U.T.M.D.Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030

Anil K. Sood Corresponding author: asood@mdanderson.org

MD Anderson Cancer Center, Houston, TX USA