Cancer and the metastatic substrate

Abstract

Seventy percent of cancer patients have detectable metastases when they receive a diagnosis and 90% of cancer deaths result from metastases. These two facts emphasise the urgency for research to study the mechanisms and processes that enable metastasis. We need to develop a greater understanding of the cellular and molecular mechanisms that cause metastasis and also we need to do more. We must also consider the micro- and macro-environmental factors that influence this disease. Studying this environmental context has led us to update the ‘seed and soil’ hypothesis which dates back to the 19th century. This theory describes cancerous cells as seeds and the substrate as the soil in target organs though this may seem antiquated. Nonetheless, the tissue specificity that researchers have recently observed in metastatic colonisation supports the validity of the seed and soil theory. We now know that the metastatic potential of a tumour cell depends on multiple, reciprocal interactions between the primary tumour and distant sites. These interactions determine tumour progression. Studies of metastasis have allowed us to develop treatments that focus on therapeutic effectiveness. These new treatments account for the frequent metastasis of some tumours to target organs such as bones, lungs, brain, and liver. The purpose of this review is first to describe interactions between the cellular and molecular entities and the target organ tumour environment that enables metastasis. A second aim is to describe the complex mechanisms that mediate these interactions.

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

“…Genetic disorders have been reported to be related to the phenotypical changes of the morphological progression sequence in the inflammation/adenoma/carcinoma (27). However, whether the aerobic glycolysis is involved in inflammation/adenoma/carcinoma sequential changes is largely unknown.…”

Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues

“…Previous studies investigating cancer development have examined various genes, including oncogenes, tumor suppressor genes, DNA repair genes, and genes encoding phase I and II enzymes (9)(10)(11)(12). GSH levels have been shown to be elevated in numerous types of human cancer, including bone marrow (13), breast (14,15) and lung (16,17).…”

K-ras Mutations as the Earliest Driving Force in a Subset of Colorectal Carcinomas

“…This strategy results in unnecessary colonoscopies; most adenomas don't progress to cancer (54), (the conversion rate is below 5%) (50), whilst a great gap is evident between the incidence of polyps (approximately 40%) (93) and that of CRC (nearly 6%) (1,4). Trying to fill the gap, we propose the detection of K-ras mutation in benign polyps: its presence implies either the carcinogenesis process has been initiated, or its progress to an advanced state has started; whatever eventuality is true, K-ras mutation reveals that a non-reversible process is in evolution and this polyp carries increased risk for being transformed to cancer.…”