Lotte Katrine Vogel
Is a cure for cancer within reach?
Research in mice has shown that over-expression of the serine protease, matriptase, single-handed causes tumors with high efficiency . Matriptase is located on the basolateral plasma membrane of all epithelial cells [2,3] and all epithelial cell derived cancers , and catalyzes the conversion of signal molecules, leading to the activation of signal transduction pathways [5,6]. Matriptase is kept under strict control by HAI-1 and HAI-2 under normal conditions [7,8]. In contrast, seventy percent of mice overexpressing matriptase in the skin developed squamous cell carcinomas, whereas mice overexpressing both matriptase and either HAI-1  or HAI-2  had a malignant cancer incidence resembling wild type mice. Similar results were obtained from another mouse study, where the tumorigenicity and metastatic capability of human prostate cancer cells were studied . It was shown that the expression of HAI-2 diminishes during prostate cancer progression and furthermore that the tumorigenicity and metastatic capability of the prostate cancer cells was reduced, when HAI-2 expression was increased . Whereas, the way by which HAI-1 and HAI-2 control matriptase remains unclear, it clearly demonstrates that HAI-1 and HAI-2 are able to control the potent oncogenic potential of matriptase.
Even more importantly, mice with already established tumors, caused by up-regulation of the matriptase expression and application of a carcinogen to the skin, showed a markedly impaired malignant progression and regression of individual tumors upon the induction of HAI-2 expression . This suggests that HAI-2 and possibly also HAI-1 may provide a way to cure cancer if supplied at the right time and place.
Matriptase, prostasin (the non-enzymatic co-activator of matriptase ), HAI-1 and HAI-2 are all synthesized on the rough endoplasmic reticulum. Matriptase , prostasin  and HAI-1  are transported along the secretory pathway to the plasma membrane , whereas HAI-2 is a resident endoplasmic reticulum-protein . Based on this it is our hypothesis that the anti-oncogenic action of HAI-1 and HAI-2 takes place in the endoplasmic reticulum since this is the only subcellular localization shared between HAI-1 and HAI-2. Furthermore, based on the homology between HAI-1 and HAI-2  and redundancy in functions [16,17], we also expect the anti-oncogenic feature to be shared by the two.
The goal of the Vogel laboratory is to provide a basic understanding of the interplay between matriptase, prostasin, HAI-1 and HAI-2 in order to use this knowledge to design treatment(s) for cancer patients.
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