This Article Order Full text via Infotrieve 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Sundberg, C. Articles by Rubin, K. Search for Related Content PubMed PubMed Citation Articles by Sundberg, C. Articles by Rubin, K.

American Journal of Pathology, Vol 143, 1377-1388, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma

C Sundberg, M Ljungstrom, G Lindmark, B Gerdin and K Rubin
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.

The expression of platelet-derived growth factor- beta (PDGF-beta) receptors in the microvasculature of human healing wounds and colorectal adenocarcinoma was investigated. Frozen sections were subjected to double immunofluorescence staining using monoclonal antibodies (MAbs) specific for pericytes (MAb 225.28 recognizing the high-molecular weight-melanoma-associated antigen, expressed by activated pericytes during angiogenesis), endothelial cells (MAb PAL- E), laminin, as well as PDGF-beta receptors (MAb PDGFR-B2) and its ligand PDGF-B chain (MAb PDGF 007). Stained sections were analyzed by computer-aided imaging processing that allowed for a numerical quantification of the degree of colocalization of the investigated antigens. An apparent background colocalization, varying between 23 and 35%, between markers for cells not expected to co-localize was recorded. This background could be due to limitations of camera resolution, to out-of-focus fluorescence, and to interdigitations of the investigated structures. In all six tumor specimens, co- localization of PDGF-beta receptors and PAL-E was not different from the background co-localization, whereas that of PDGF-beta receptors and high-molecular weight-melanoma-associated antigen was significantly higher with mean values between 57 and 71%. Qualitatively, the same pattern was obtained in the two investigated healing wounds. PDGF-B chain did not co-localize with either PAL-E or high-molecular weight- melanoma-associated antigen, but PDGF-B chain-expressing cells were, however, frequently found juxtaposed to the microvasculature. The expression of PDGF-beta receptors on pericytes in activated microvessels and the presence of PDGF-B chain-expressing cells in close proximity to the microvasculature of healing wounds and colorectal adenocarcinoma is compatible with a role for PDGF in the physiology of the microvasculature in these conditions.

This article has been cited by other articles:

				T. Kuwai, T. Nakamura, S.-J. Kim, T. Sasaki, Y. Kitadai, R. R. Langley, D. Fan, S. R. Hamilton, and I. J. Fidler Intratumoral Heterogeneity for Expression of Tyrosine Kinase Growth Factor Receptors in Human Colon Cancer Surgical Specimens and Orthotopic Tumors Am. J. Pathol., February 1, 2008; 172(2): 358 - 366. [Abstract] [Full Text] [PDF]

				L. Q.M. Chow and S. G. Eckhardt Sunitinib: From Rational Design to Clinical Efficacy J. Clin. Oncol., March 1, 2007; 25(7): 884 - 896. [Abstract] [Full Text] [PDF]

				M. L. Tejada, L. Yu, J. Dong, K. Jung, G. Meng, F. V. Peale, G. D. Frantz, L. Hall, X. Liang, H.-P. Gerber, et al. Tumor-Driven Paracrine Platelet-Derived Growth Factor Receptor {alpha} Signaling Is a Key Determinant of Stromal Cell Recruitment in a Model of Human Lung Carcinoma. Clin. Cancer Res., May 1, 2006; 12(9): 2676 - 2688. [Abstract] [Full Text] [PDF]

				A. Liden, A. Berg, T. Nedrebo, R. K. Reed, and K. Rubin Platelet-Derived Growth Factor BB-Mediated Normalization of Dermal Interstitial Fluid Pressure After Mast Cell Degranulation Depends on {beta}3 but Not {beta}1 Integrins Circ. Res., March 17, 2006; 98(5): 635 - 641. [Abstract] [Full Text] [PDF]

				U. Ozerdem, K. Alitalo, P. Salven, and A. Li Contribution of Bone Marrow-Derived Pericyte Precursor Cells to Corneal Vasculogenesis Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3502 - 3506. [Abstract] [Full Text] [PDF]

				R. Virmani, F. D. Kolodgie, A. P. Burke, A. V. Finn, H. K. Gold, T. N. Tulenko, S. P. Wrenn, and J. Narula Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2054 - 2061. [Abstract] [Full Text] [PDF]

				S. H. Lee, D. Lopes de Menezes, J. Vora, A. Harris, H. Ye, L. Nordahl, E. Garrett, E. Samara, S. L. Aukerman, A. B. Gelb, et al. In vivo Target Modulation and Biological Activity of CHIR-258, a Multitargeted Growth Factor Receptor Kinase Inhibitor, in Colon Cancer Models Clin. Cancer Res., May 15, 2005; 11(10): 3633 - 3641. [Abstract] [Full Text] [PDF]

				M. Furuhashi, T. Sjoblom, A. Abramsson, J. Ellingsen, P. Micke, H. Li, E. Bergsten-Folestad, U. Eriksson, R. Heuchel, C. Betsholtz, et al. Platelet-Derived Growth Factor Production by B16 Melanoma Cells Leads to Increased Pericyte Abundance in Tumors and an Associated Increase in Tumor Growth Rate Cancer Res., April 15, 2004; 64(8): 2725 - 2733. [Abstract] [Full Text] [PDF]

				S. M. Apte, D. Fan, J. J. Killion, and I. J. Fidler Targeting the Platelet-Derived Growth Factor Receptor in Antivascular Therapy for Human Ovarian Carcinoma Clin. Cancer Res., February 1, 2004; 10(3): 897 - 908. [Abstract] [Full Text] [PDF]

				A. N. Witmer, B. C. van Blijswijk, C. J.F. van Noorden, G. F.J.M. Vrensen, and R. O. Schlingemann In Vivo Angiogenic Phenotype of Endothelial Cells and Pericytes Induced by Vascular Endothelial Growth Factor-A J. Histochem. Cytochem., January 1, 2004; 52(1): 39 - 52. [Abstract] [Full Text] [PDF]

				T. J. Abrams, L. J. Murray, E. Pesenti, V. Walker Holway, T. Colombo, L. B. Lee, J. M. Cherrington, and N. K. Pryer Preclinical evaluation of the tyrosine kinase inhibitor SU11248 as a single agent and in combination with "standard of care" therapeutic agents for the treatment of breast cancer Mol. Cancer Ther., October 1, 2003; 2(10): 1011 - 1021. [Abstract] [Full Text]

				K. Pietras, M. Stumm, M. Hubert, E. Buchdunger, K. Rubin, C.-H. Heldin, P. McSheehy, M. Wartmann, and A. Ostman STI571 Enhances the Therapeutic Index of Epothilone B by a Tumor-selective Increase of Drug Uptake Clin. Cancer Res., September 1, 2003; 9(10): 3779 - 3787. [Abstract] [Full Text] [PDF]

				D. B. Mendel, A. D. Laird, X. Xin, S. G. Louie, J. G. Christensen, G. Li, R. E. Schreck, T. J. Abrams, T. J. Ngai, L. B. Lee, et al. In Vivo Antitumor Activity of SU11248, a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial Growth Factor and Platelet-derived Growth Factor Receptors: Determination of a Pharmacokinetic/Pharmacodynamic Relationship Clin. Cancer Res., January 1, 2003; 9(1): 327 - 337. [Abstract] [Full Text] [PDF]

				X. Huang, M. K. Wong, H. Yi, S. Watkins, A. D. Laird, S. F. Wolf, and E. Gorelik Combined Therapy of Local and Metastatic 4T1 Breast Tumor in Mice Using SU6668, an Inhibitor of Angiogenic Receptor Tyrosine Kinases, and the Immunostimulator B7.2-IgG Fusion Protein Cancer Res., October 15, 2002; 62(20): 5727 - 5735. [Abstract] [Full Text] [PDF]

				S. Morikawa, P. Baluk, T. Kaidoh, A. Haskell, R. K. Jain, and D. M. McDonald Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors Am. J. Pathol., March 1, 2002; 160(3): 985 - 1000. [Abstract] [Full Text] [PDF]

				K. Pietras, A. Östman, M. Sjöquist, E. Buchdunger, R. K. Reed, C.-H. Heldin, and K. Rubin Inhibition of Platelet-derived Growth Factor Receptors Reduces Interstitial Hypertension and Increases Transcapillary Transport in Tumors Cancer Res., April 1, 2001; 61(7): 2929 - 2934. [Abstract] [Full Text]

				C. Sundberg, J. A. Nagy, L. F. Brown, D. Feng, I. A. Eckelhoefer, E. J. Manseau, A. M. Dvorak, and H. F. Dvorak Glomeruloid Microvascular Proliferation Follows Adenoviral Vascular Permeability Factor/Vascular Endothelial Growth Factor-164 Gene Delivery Am. J. Pathol., March 1, 2001; 158(3): 1145 - 1160. [Abstract] [Full Text] [PDF]

				A. D. Laird, P. Vajkoczy, L. K. Shawver, A. Thurnher, C. Liang, M. Mohammadi, J. Schlessinger, A. Ullrich, S. R. Hubbard, R. A. Blake, et al. SU6668 Is a Potent Antiangiogenic and Antitumor Agent That Induces Regression of Established Tumors Cancer Res., August 1, 2000; 60(15): 4152 - 4160. [Abstract] [Full Text]

				L. M. Strawn, F. Kabbinavar, D. P. Schwartz, E. Mann, L. K. Shawver, D. J. Slamon, and J. M. Cherrington Effects of SU101 in Combination with Cytotoxic Agents on the Growth of Subcutaneous Tumor Xenografts Clin. Cancer Res., July 1, 2000; 6(7): 2931 - 2940. [Abstract] [Full Text]

				C.-H. Heldin and B. Westermark Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor Physiol Rev, October 1, 1999; 79(4): 1283 - 1316. [Abstract] [Full Text] [PDF]

				T. A. T. Fong, L. K. Shawver, L. Sun, C. Tang, H. App, T. J. Powell, Y. H. Kim, R. Schreck, X. Wang, W. Risau, et al. SU5416 Is a Potent and Selective Inhibitor of the Vascular Endothelial Growth Factor Receptor (Flk-1/KDR) That Inhibits Tyrosine Kinase Catalysis, Tumor Vascularization, and Growth of Multiple Tumor Types Cancer Res., January 1, 1999; 59(1): 99 - 106. [Abstract] [Full Text] [PDF]