The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation

Department of Surgery, McGill University Health Cener and Royal Victoria Hospital, Quebec, Canada.
American Journal Of Pathology (Impact Factor: 4.6). 06/2007; 170(5):1781-92. DOI: 10.2353/ajpath.2007.060886
Source: PubMed

ABSTRACT Inflammation can play a regulatory role in cancer progression and metastasis. Previously, we have shown that metastatic tumor cells entering the liver trigger a proinflammatory response involving Kupffer cell-mediated release of tumor necrosis factor-alpha and the up-regulation of vascular endothelial cell adhesion receptors, such as E-selectin. Here, we analyzed spatio-temporal aspects of the ensuing tumor-endothelial cell interaction using human colorectal carcinoma CX-1 and murine carcinoma H-59 cells and a combination of immunohistochemistry, confocal microscopy, and three-dimensional reconstruction. E-selectin expression was evident mainly on sinusoidal vessels by 6 and 10 hours, respectively, following H-59 and CX-1 inoculation, and this corresponded to a stabilization of the number of tumor cells within the sinuses. Tumor cells arrested in E-selectin(+) vessels and appeared to flatten and traverse the vessel lining, away from sites of intense E-selectin staining. This process was evident by 8 (H-59) and 12 (CX-1) hours after inoculation, coincided with increased endothelial vascular cell adhesion molecule-1 expression, and involved tumor cell attachment in areas of intense vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 expression. Nonmetastatic (human) MIP-101 and (murine) M-27 cells induced a weaker response and could not be seen to extravasate. The results show that metastatic tumor cells can alter the hepatic microvasculature and use newly expressed endothelial cell receptors to arrest and extravasate.

Download full-text


Available from: Pnina Brodt, Apr 06, 2015
  • Source
    • "While the role of integrin in cancer progression is mainly associated with tumor cell invasion and tumor induced angiogenesis, integrins can play a direct role in tumor cell adhesion to the intravascular endothelium. For example, metastatic breast cancer cells deficient in integrin β1 expression fail to attach and transmigrate through the vessel endothelium [27] [53]. Furthermore, over-expression of neuropilin-2 non-kinase receptor (NPR-2) in cancer cells promotes successful attachment in an α5 integrin-dependent manner. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metastasis is the main cause of prostate cancer-associated deaths. While significant progress has been made in the treatment of primary tumors, efficient therapies that target the metastatic spread of prostate cancer are far from clinical reality. To efficiently treat cancer we need be able to impede its spread. Unfortunately, the majority of current therapeutics approved to treat metastatic cancer were originally selected based on their ability to inhibit primary tumor growth. This inherent flaw precludes these therapies from efficiently targeting the development of secondary metastatic lesions, a process that is distinct from that of primary tumor progression. In this review we will summarize the conceptual, cellular and molecular targets that should be considered to design effective anti-metastatic therapies.
  • Source
    • "In all cases reported of TC metastatic to oral cavity, the gingiva is affected. Some authors suggest the preference of metastasis to reach the attached gingiva in the presence of chronic gingivitis because the rich vascularity of the inflammatory process would allow trapping of tumour cells and thus being fertile site to spread most of the metastatic process (Auguste et al., 2007). Chronic inflammation is known to play a role in cancer initiation, promotion, and metastasis (Das Roy et al., 2012). "
    International Journal of Morphology 03/2013; 31(1):140-143. · 0.20 Impact Factor
  • Source
    • "Type II consists of groups too small (<6 cells) to be cohorts by the Christofori definition, but are not single cells. Such small groups have been documented in vivo [36] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumour cells employ a variety of mechanisms to invade their environment and to form metastases. An important property is the ability of tumour cells to transition between individual cell invasive mode and collective mode. The switch from collective to individual cell invasion in the breast was shown recently to determine site of subsequent metastasis. Previous studies have suggested a range of invasion modes from single cells to large clusters. Here, we use a novel image analysis method to quantify and categorise invasion. We have developed a process using automated imaging for data collection, unsupervised morphological examination of breast cancer invasion using cognition network technology (CNT) to determine how many patterns of invasion can be reliably discriminated. We used Bayesian network analysis to probabilistically connect morphological variables and therefore determine that two categories of invasion are clearly distinct from one another. The Bayesian network separated individual and collective invading cell groups based on the morphological measurements, with the level of cell-cell contact the most discriminating morphological feature. Smaller invading groups were typified by smoother cellular surfaces than those invading collectively in larger groups. Interestingly, elongation was evident in all invading cell groups and was not a specific feature of single cell invasion as a surrogate of epithelial-mesenchymal transition. In conclusion, the combination of cognition network technology and Bayesian network analysis provides an insight into morphological variables associated with transition of cancer cells between invasion modes. We show that only two morphologically distinct modes of invasion exist.
    Analytical cellular pathology (Amsterdam) 01/2011; 34(1-2):35-48. DOI:10.3233/ACP-2011-0003 · 1.76 Impact Factor
Show more