Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer

Li, Chenggang; Guo, Baoqiang; Wilson, Philip B.; Stewart, Alan L.; Byrne, Ged; Bundred, Nigel; Kumar, Shant

doi:10.1002/(sici)1097-0215(20000320)89:2<122::aid-ijc4>3.0.co;2-m

Cited by 129 publications

(88 citation statements)

References 27 publications

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“…Raised levels of CD105 and TGFb3 were found in plasma samples from colorectal cancer patients, which are in agreement with previous observations (Li et al, 1998(Li et al, , 2000b. Published data indicate that CD105 is strongly expressed in blood vessels in cancer tissues but weakly in normal tissues.…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, it is reasonable to assume that increased CD105 in the circulation of patients with cancer resulted from angiogenesis both within and in the immediate vicinity of the tumour mass. That CD105 levels were positively correlated with a Dukes' stage, was entirely consistent with the observation in patients with breast cancer, wherein significantly elevated CD105 levels were found in patients who subsequently relapsed or developed metastatic disease (Li et al, 2000b). A recent publication also supports the conclusion that patients with lymph node metastasis possess markedly elevated CD105 levels in the circulation (Takahashi et al, 2001).…”

Section: Discussionsupporting

confidence: 71%

“…Soluble CD105 was measured using an indirect sandwich ELISA (Li et al, 2000b), wherein purified Mab E9, which specifically reacts with CD105, and biotinylated Mab E9, in conjunction with streptavidin peroxidase, were used as capture and detection reagent, respectively. White microtitre plates were coated with Mab E9 (100 ml well À1 ) diluted 1 : 1000 (1 mg ml À1 ) in 0.1 M PBS and incubated overnight at 4 o C. The coated plates were blocked using 1% BSA and PBS -Tween for 2 h at room temperature.…”

Section: Immunohistochemical Staining Of Tgfb1 and Tgfb3mentioning

confidence: 99%

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Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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CD105 and its ligand transforming growth factor b (TGFb) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40 -9.00) and 3.10 (range 0.90 -8.00), respectively. Kaplan -Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFb1 and TGFb3 together with the receptor -ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFb1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFb1 level was noted in patients with carcinoma over the controls. Furthermore, TGFb3 and CD105/ TGFb3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFb1 was expressed in cancer cells but TGFb3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFb1, TGFb3 and CD105/TGFb complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 71%

Section: Immunohistochemical Staining Of Tgfb1 and Tgfb3mentioning

confidence: 99%

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Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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“…Soluble endoglin has been reported to rise in plasma of breast cancer patients who developed metastases as compared to both normal controls and cancer patients without distant spread [29]. Elevated serum endoglin was associated with distant metastases not only in breast, but also in colorectal cancer and in other solid tumors [19].…”

Section: Discussionmentioning

confidence: 99%

Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

Myśliwiec¹,

Pawlak²,

Kukliński³

et al. 2009

Folia Histochem Cytobiol.

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Abstract:Colorectal cancer growth and spread is absolutely dependent on angiogenesis with vascular endothelial growth factor (VEGF) being the most important cytokine involved in the process. Endoglin, a membrane co-receptor for TGF-β, has recently emerged as a sensitive index of cancer stage. There is now sufficient evidence indicating that microvessel density assessed by endoglin-immunostaining correlates with stage of colorectal cancer and patient survival. An association of a soluble form of endoglin with lymph node and distant metastases has recently been reported in two studies. Both of them used local elaborated immunoassays for endoglin assessment. The aim of our study was to determine the efficacy of plasma endoglin, assessed using a commercial kit, as a marker of tumor spread and distant metastases in colorectal cancer patients. We studied 48 colorectal cancer patients, compared with 22 healthy subjects, using ELISA. We observed that colorectal cancer patients had increased plasma VEGF-A, but not endoglin levels. However, we found an association of plasma endoglin with the stage of malignancy. Endoglin levels were increased in metastasis-positive patients when compared to both metastasis-negative patients and healthy volunteers. Plasma endoglin correlated with VEGF-A, CEA and CA19.9. Endoglin assessment in plasma does not seem useful as a maker of colorectal cancer. Our observations indicate however that it might be helpful in selecting patients with metastatic disease.

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“…[35][36][37][38][39] Therefore, apart from HHT1, targeting endoglin expression to the vasculature might be useful to study the pathologies listed above, which are associated with endoglin up-regulation, as well as to investigate the role of endoglin in the normal vascular physiology. Interestingly, the expression of endoglin in the tumor neovasculature has been used to design immunotoxins specific for endoglin as an anti-angiogenic treatment for solid tumors; 36,40 it also suggests that the endoglin promoter could be used to deliver angiogenesis inhibitors in line with the proposed anti-angiogenic strategy to starve solid tumors.…”

Section: Figure 6 Immunohistochemical Detection Of Endoglin Upon Locamentioning

confidence: 99%

Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters

et al. 2001

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Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer

Cited by 129 publications

References 27 publications

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters

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