As periodic acid-Schiff reaction positive loops and networks indicating micro vascular channels within melanoma have been described. As these microvascular channels are lined by the melanoma cells themselves and are not covered by endothelial cells, this apical surface might provide additional space for CEACAM expression. A further reason for the difference in expression can be found in tumour – stroma interactions. Cancer cells in a tumour xenograft are exposed to mouse extracellular matrix and mouse cells like blood vessel endothelia, lymphocytes and macrophages and also to mouse hormones. All these tumor-stroma interactions can potentially alter the expression of genes in the human tumour cell in xenografts. The few regions of higher CEACAM expression in vivo in the xenograft of cell line T47D could be explained by the fact, that hypoxia could upregulate CEACAM expression via HIF1a signaling. A HIFa response element is located in the promoter region of CEACAM. Another factor to be investigated is the accessibility of the monoclonal antibody to the CEACAM binding sites after i.v. application of the T84.1 antibody. Using labelled lectins as a probe, we have previously shown that vast differences in lectin binding site accessibility existed between the binding of the lectins to tissue sections and to the same tissue after i.v. injection of the same lectins. We therefore investigated the presence of CEACAM binding sites in vivo using the CEACAM specific T84.1 mAB on FEMX-1 cells after its i.v. application. FEMX-1 cells were chosen as they readily grow in SCID mice and additionally show robust CEACAM expression in vitro and in vivo. We could indeed show that the i.v. applied antibody reaches the target, but to a moderate extent only as its presence was limited to the direct vicinity of blood vessels. Furthermore, melanoma is a particularly well suited malignancy to be investigated as CEACAM expression is positively correlated with metastasis formation. Therefore more malignant cells express CEACAM-1 in melanoma, while in other tumour entities such as breast or prostate cancer CEACAM-1 expression is downregulated during malignant progression. A known phenomenon of tumour xenografts is the uneven distribution of blood vessels within different areas of the tumour. In our FemX-1 melanoma model the vascular density was more intense in the periphery than in the centre of the tumour xenograft. The access of the T84.1 antibodies was limited to areas around blood vessels, resembling Kroghs’ cylinder which shows the limits of Evofosfamide oxygen diffusion in tissues. Even the Evans Blue-Albumin complex with a lower mass weight of 67 kDa could only be found in the same area, as the injected T84.1 antibody. All transport processes beyond this cylinder are not based on diffusion but on convection. Convection, however, is severely altered in tumours because of the absence of functional lymphatic vessels within the tumour. This leads to an accumulation of interstitial fluid within tumours resulting in a high interstitial fluid pressure of tumours.