Metastatic tumor cells

Tumor classification — Drug treatment regimes often depend upon tumor type. The origins of metastatic tumor cells can be difficult to determine by conventional histopathology. Gene expression profiling may complement the more traditional methodologies where tumors are difficult to classify. 

Mastro AM, Vogler EA (2009) A three-dimensional osteogenic tissue model for the study of metastatic tumor cell interactions with bone. Cancer Res 69 4097 100... 

Henderson BR, Tansey WP, Phillips SM, Ramshaw IA, Kefford RF. Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells. Cancer Res 1992 52 2489-2496. 

PI 1. Pfung, B. R., Onoda, M., Lynch, J. H., and Djakiew, D., Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue of expression in four human metastatic tumor cell lines. Cancer Res. 52,5403-5406 (1992). 

Beside adhesion per se, tumor cell interactions with ECM components influence motility, invasiveness and many other important aspects of the metastatic tumor cell phenotype. Tumor cell motility and adhesion are, in fact, closely linked, thus implicating a role for tumor cell adhesion in invasion. Indeed, tumor cell invasion has been proposed to represent a three step process, involving tumor cell adhesion, release of ECM degrading enzymes and tumor cell... 

The finding that metastatic tumor cells can secrete enzymes that degrade BM collagen has provided indirect evidence that these cells have the capability to damage the structural component of the BM... 

The autocrine production of growth factors may give metastatic tumor cells an intrinsic advantage to establish a growth at most of the organs in which they can efficiently lodge. No correlations... 

Note This list of tumors is not exhaustive and is provided only as a resource to identify some commonly used metastatic tumor cell lines. 

Li, L., Nicolson, G. L. and Fidler, I. J. (1991). Direct in vitro lysis of metastatic tumor cells hy cytokine-activated murine vascular endothelial cells. Cancer Res. 51, 245-254. 

Netland, P. A. and Zetter, B. R. (1984). Organ-specific adhesion of metastatic tumor cells in vitro. Science 224, 1113-1115. 

Raz, A., Hanna, N. and Fidler, I. J. (1981). In vivo isolation of a metastatic tumor cell variant involving selective and nonadaptive processes. J. Natl. Cancer Inst. 66, 183-189. 

Voura EB, Jaiswal JK, Mattoussi H, Simon SM. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat Med 2004 10 993-998. 

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...

As shown in Fig. (5) , primary tumor cells in the spleen grew and invaded the while and red pulp of the spleen in mice with intrasplenically implanted LLC. The orally administered triterpenoid fractions (100 or 200 mg/kg) prevented the tumor growth and the invasion of the white pulp of the spleen. Furthermore, the orally administered triterpenoid fractions induced an accumulaiion of lymphocytes around tumor cells in the white pulp of the spleen Fig. (5) . The metastatic tumor cells in the liver also grew and invaded the hepatocytes in mice with intrasplenically implanted... 

LLC. The growth of the metastatic tumor cells was prevented by the orally administered triterpenoid fractions Fig. (6a) . Lymophocytes in the liver also accumulated around the metastatic tumor cells Fig. (6b) . 

Khatib AM, Kontogiannea M, Fallavollita L, Jamison B, Meterissian S, Brodt P. Rapid induction of cytokine and E-selectin expression in the liver in response to metastatic tumor cells. Cancer Res 1999 59 1356-13561. 

Pirollo et al. developed a nanoimmunoliposome modified with anti-TfR scFV to deliver siRNA to tumor cells. A fluorescein-labeled siRNA was delivered via systemic injection and it was specifically distributed into primary and metastatic tumor cells [110]. Later, the authors developed a similar nanoimmunoliposome for an anti-Her-2 siRNA. To enhance the endosomal release, a pH-sensitive histidine-lysine peptide was included in the complex. The in vitro results showed that the complexes can sensitize human cancer cells to che-motherapeutics. Furthermore, systemic delivery of the siRNA significantly inhibit tumor growth in a pancreatic cancer model [109]. 

Given our recent observations and the observations of others, we can conclude that the nonrandom expression of chemokine receptors in tumor cells is pivotal in determining the metastatic destination of these cells. In such a model, metasta-ses are actually very difficult to become established, as metastatic tumor cells have to form a beachhead to successfully proliferate and invade. It is likely that chemokines play a central role, along with other adhesion molecules, in cancer metastasis. 

Studies in our laboratory have found similar results with NSCLC cell lines (unpublished observations). These findings support the notion that certain chemokine ligand(s) and their receptors orchestrate precise and preferential destination of metastatic tumor cells to specific organs. 

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