Hematogenous metastasis

Variations on the filter-based assay have been designed to approximate more physiological contexts. Such assays include tumor cell invasion across a confluent cell monolayer (e.g., endothelial cells (EC) as a surrogate for intravasation or extravasation during hematogenous metastasis (24)) and ovarian carcinoma invasion of mesothelial cell monolayers (25). Additionally, 1 mm thick slices of human brain tissue have been used as a tissue barrier on Transwell filters with invasion of GFP-labeled glioma cells measured by confocal microscopy (26). 

Yonenaga Y, Mori A, Onodera H, Yasuda S, Oe H, Fujimoto A, et al. Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients. Oncology 2005 69 159-166. 

Metastasis is defined as the formation of tumors that are discontinuous from the primary tumor. These secondary tumors can be at nearby or distant sites and can form following dissemination of cells via lymphatic, hematogenous, coelomic cavities or epithelial cavities (Willis, 1973). The most common routes for metastatic spread are lymphatic and hematogenous metastasis so, secondary tumor formation via those routes will be the focus in this chapter. However, it must be noted that these routes are not necessarily the common ones for the spread of some tumor types (e.g. ovary (Cannistra, 1993)). 

Kannagi, R. (1997). Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconj. J. 14, 577-584. 

Morris, V. L., Schmidt, E. E., MacDonald, I. C., Groom, A. C. and Chambers, A. F. (1997). Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy. Invasion Metastasis 17, 281-296. 

Taraboletti, G., Belotti, D., Giavazzi, R., Sobel, M. E. and Castronovo, V. (1993). Enhancement of metastatic potential of murine and human melanoma cells by laminin receptor peptide G attachment of cancer cells to subendothelial matrix as a pathway for hematogenous metastasis. J. Natl. Cancer Inst. 85, 235-240. 

Intraoperative molecular detection of circulating tumor cells by reverse transcription-polymerase chain reaction in patients with bihary-pancreatic cancer is associated with hematogenous metastasis. Ann Surg Oncol, 9, 364—370. 

Several studies have indicated that selectins also recognize cancer cells and therefore facilitate hematogenic metastasis. Overexpression of E-selectin in the liver of transgenic mice leads to redirection of melanoma cells in this organ (Biancone et al. 1996). Specific targeting E-selectin with antibodies has been shown to significantly... 

Hematogenous metastasis to the adrenal glands is common, exceeded in frequency only by metastasis to the lung, liver, and bone. Autopsies have documented... 

Weiss, L., Nanmnark, U., Johansson, B.R., and Bagge, U. (1992). Lethal deformation of cancer cells in the microcirculation a potential rate regulator of hematogenous metastasis. Int. J. Cancer 50(1), 103-107. 

Tl. Tanaka, N., Ogawa, H., Tanaka, K., Kingo, M., and Kohga, S., Effects of tranexamic acid and urokinase on hematogenous metastases of Lewis lung carcinoma in mice. Invasion Metastasis I, 149-157 (1991). 

Palumbo, J. S., Potter, J. M., Kaplan, L. S., Talmage, K., Jackson, D. G., and Degen, J. L. (2002). Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res. 62, 6966-6972. 

The two primary pathways of metastasis are hematogenous and lymphatic. Other, less-common modes of disease spread include dissemination via cerebrospinal fluid and transabdominal spread within the peritoneal cavity. Tumors are constantly shedding neoplastic cells into the systemic circulation or surrounding lymphatics. This process may begin early in the hfe of the tumor and often increases with time. The time course for metastasis depends largely on the biology of the tumor. Breast cancer, for example, tends to metastasize very early. Not all of the shed cancer cells, or seeds, result in a metastatic lesion. The seed must first find the appropriate soU, or an environment suitable for growth. This process is illustrated in the diverse patterns... 

The involvement of platelets in assisting hematogenous spread of metastatic tumor cells and the interactions between platelets, cancer cells, and the blood vessel wall were proposed decades ago. This was confirmed in experimental model systems of thrombocytopenia which showed inhibition of metastasis (Gasic et al., 1973 Kimoto et al., 1993). Honn et al, proposed the first hypothesis on the involvement of bioactive lipid mediators, specifically TXA2... 

Fig. 6.3 Eicosanoids and Tumor-platelet interactions in metastasis and the role of 12-HETE in tumor cell extravasation. Studies have clearly shown that hematogenous route of metastasis spread of cancer cells, involves interactions with platelets. Tumor-platelet interactions and subsequent aggregation is critically controlled by a delicate balance between the level of endothelium derived PGI2 and platelet or tumor derived TXA2. Elevated TXA2 levels in the circulation can tip the balance towards platelet aggregation and tumor metastasis to distant organs, whereas increases in PGI2 levels can block this interaction preventing spread of cancer cells. Shown in this illustration is a schematic of a blood vessel, with metastatic tumor cells interacting with platelets. Interactions of tumor cells with platelets and endothelial cells have been demonstrated to induce 12(S)-HETE production, which leads to retraction of endothelial cell layers enabling metastatic tumor cells to extravasate and set up secondary colonies of metastasis...

Nakamura, BC, K. Konoha, Y. Yamaguchi, et al. 2003. Combined effects of Cordyceps sinensis and methotrexate on hematogenic lung metastasis in mice. Receptors Channels 9(5) 329-334. 

Recurrent cervical cancer is associated with bone metastases (Fig. 7.39) in 15%-29% of patients at autopsy [ too, 103]. Typical locations are the bony pelvis as well as the lumbar and other vertebral bodies. Bone metastases in the ribs and extremities are less common. Skeletal metastases typically have an osteolytic character and originate from locally advanced or recurrent tumor in the pelvic sidewall or arise through retrograde tumor spread in patients with para-aor-tic lymph node metastasis [104]. Hematogenous dissemination to the skeleton occurs late. MRl with unenhanced and contrast-enhanced fat-saturated Tl-weighted sequences depicts bone metastases as hyperintense lesions in the low-intensity bone marrow with a high sensitivity. CT primarily shows the extent of osseous destruction. 

Weiss L (1992) Comments on hematogenous metastatic patterns in humans as revealed by autopsy. Clin Exp Metastasis 10 191 199... 

Hematogenous spread from various primary tumours, mainly malignant melanoma, bronchogenic and breast carcinoma, may metastasize to the duodenum or diff use wall thickening (see Fig. 6.1.24). A metastasis may be seen on CT as an intraluminal soft tissue mass. Larger metastases often demonstrate intratumoral necrosis or cavitation, indistinguishable from lymphoma or leiomyosarcoma (JAYARAMAN et al. 2001) Zissin et al. 2002). 

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