Previously, tumors were thought to have six characteristics: immortality, migratory nature, loss of contact inhibition, self-sufficiency of growth signals, escape to programmed cell death, and the ability to grow blood vessels. Recent studies suggest that tumors also possess a seventh characteristic: tumor-associated inflammation. Malignant tumors are characterized by their ability to metastasize, that is, to invade anatomically distant normal tissues where they are inoculated and grow. In this complex and highly selective process, tumor cells leave their original site of growth and spread through different pathways such as the bloodstream and lymphatic vascular pathways. Not all tumor cells can metastasize, as successful metastasis relies on the intrinsic characteristics of the tumor cells and a number of factors derived from the tumor microenvironment. For example, the microenvironment provides the blood vessels and lymphatic vessels within or around the tumor, an inflammatory environment including immune cells and their secretory products, and a scaffold in the form of extracellular matrix that can provide further growth. Regarding this aspect, Kim et al. have unexpectedly identified molecular pathways linking the validation and metastasis of the tumor microenvironment. The association between inflammation and tumor was well elucidated in. Several inflammatory diseases, including inflammatory bowel disease, increase the risk of tumors. Conversely, in tumors that are not associated with apparent inflammation in an epidemiological sense (e.g. breast cancer), activation of oncogenes leads to the production of inflammatory molecules and the aggregation of inflammatory cells. In the tumor microenvironment, inflammatory cells and molecules influence almost every aspect of tumor progression, including the ability of tumor cells to metastasize. In 2000, Hanahan and Weinberg5 proposed a model of six characteristics that tumors possess. They were unrestricted replicative capacity, the ability to grow blood vessels (angiogenesis), escape to programmed cell death, self-sufficiency of growth signals, insensitivity to growth inhibitors, tissue invasion and metastasis. the findings of Kim and colleagues2, together with studies3,4, suggest that this model should be revised to add tumor-associated inflammation as another of its features. A group of cytokine proteins, including IL-1, IL-6, TNF and RANKL, activate inflammation and are thought to increase the metastatic capacity of tumor cells by acting on several steps associated with cellular dissemination and implantation at secondary sites. The key transcription factor downstream of inflammatory factors, NF-kappaB, is activated by these factors and promotes inflammation.3 The major source of inflammatory factors in the tumor microenvironment is specialized leukocytes that become macrophages. Tumor-associated macrophages assist in the malignant behavior of tumor cells not only by producing cytokines but also by secreting growth factors and stromal interpretative enzymes. Kim et al. explored the molecular pathways linking tumor molecules, macrophages and metastasis relationships. By purifying the stromal components of tumor cell (Lewis lung cancer cell line) growth, they isolated a factor that induces cytokine production by macrophages. They identified this tumor-derived macrophage activator as a multifunctional proteoglycan, a component protein of the extracellular matrix that is frequently upregulated in human tumors. The authors found that the multifunctional proteoglycan was recognized by TLR2 and TLR6, two receptor proteins belonging to a family of microbial-derived molecules and cellular receptors for tissue destruction. They went on to silence the multifunctional glycoproteins using RNA interference techniques and with TNF and TLR-deficient mice. On the basis of the evidence obtained, the authors propose that, in a model of Lewis lung cancer, tumor-derived multifunctional proteoglycans act on macrophages via TLR2/TLR6, thereby producing inflammatory factors that enhance metastasis. Kim and colleagues’ observations flirt with the importance of the extracellular matrix in tumor-associated inflammation. The stroma acts as a storage site for cytokines and growth factors, particularly vascular endothelial growth factor, which is mobilized by enzymes produced by inflammatory leukocytes and promotes angiogenesis during tumor progression. In addition, immune cells called B cells quietly pool inflammation by producing antibodies that accumulate in the extracellular matrix during tumor progression caused by human papillomavirus virus. Furthermore, macrophage-derived extracellular matrix proteins known as SPARC predispose tumors to motility and metastasis. Thus, it appears that the extracellular matrix component not only acts as a scaffold or an enzymatic substrate during tumor invasion, but is a central component of tumor-associated inflammation. The current study offers the unexpected prospect of linking molecular pathways that acquire metastatic capacity during inflammation and tumor progression. Evaluating the importance of multifunctional proteoglycans and other extracellular matrix proteins in models to respond to the diversity of human tumors is imperative, and a new page in tumor treatment strategies may be turned with this work.