| 1. |
- Lindmark, G, et al.
(author)
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Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer : relation to survival.
- 1993
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In: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 19:1, s. 50-60
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Journal article (peer-reviewed)abstract
- The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.
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| 2. |
- Reuterdahl, C, et al.
(author)
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Characterization of platelet-derived growth factor beta-receptor expressing cells in the vasculature of human rheumatoid synovium
- 1991
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In: Laboratory Investigation. - 1530-0307. ; 64:3, s. 321-329
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Journal article (peer-reviewed)abstract
- Platelet-derived growth factor (PDGF) beta-receptor expression in normal and rheumatoid synovia was investigated by double immunofluorescence staining of frozen sections and by in situ hybridization. In the inflamed synovia, PDGF beta-receptor mRNA was present in vascular cells, as well as in discrete stromal cells. PDGF beta-receptor expressing cells in rheumatoid synovia were characterized by double immunofluorescence staining using the PDGFR-B2 monoclonal antibody at a concentration at which this antibody merely stained granular accumulations of PDGF beta-receptors. Granular accumulations of PDGF beta-receptors were articulate in blood vessel cells, but also appeared in discrete stromal cells. Thus, the overall distribution of cells having granular accumulations of PDGF beta-receptors was similar to the distribution of cells expressing PDGF beta-receptor mRNA. Double immunofluorescence stainings showed that: (a) a majority (greater than 90%) of resident macrophages did not express granular PDGF beta-receptor staining, but macrophages were often juxtaposed to PDGF beta-receptor-positive cells; (b) T lymphocytes did not express PDGF beta-receptors, but these cells were frequently found in the proximity of cells stained by PDGFR-B2; (c) in some blood vessels both HLA-DR expressing cells and PDGF beta-receptor expressing cells could be visualized, whereas in other blood vessels, cells expressing only one of these activation markers could be detected; (d) smooth muscle cells in blood vessels contained PDGF beta-receptors; and (e) capillary endothelial cells in the inflamed synovia recurrently displayed granular PDGF beta-receptor staining. The granular accumulations of PDGF beta-receptors may reflect internalization of the receptor as a result of paracrine or autocrine ligand stimulation. In support of such a possibility are the findings that elevated levels of PDGF B chain mRNA were detected by in situ hybridization in the inflamed synovia, and that cells expressing PDGF B chain mRNA were distributed similarly to cells expressing PDGF beta-receptor mRNA. Taken together, the results indicate that PDGF has a role in the inflammatory process in rheumatoid synovitis, most likely by stimulating proliferative events in the vasculature.
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| 3. |
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| 4. |
- Lindmark, G, et al.
(author)
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Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.
- 1993
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In: Laboratory Investigation. - 0023-6837 .- 1530-0307. ; 69:6, s. 682-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear.EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively.RESULTS: All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome.CONCLUSIONS: The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.
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| 5. |
- Reuterdahl, C, et al.
(author)
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Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans
- 1993
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 91:5, s. 2065-2075
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Journal article (peer-reviewed)abstract
- The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled.
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