A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate.

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.

A review of stem cell translation and potential confounds by cancer stem cells.

Mesenchymal stem cells (MSCs) are multipotent cells found in both fetal and adult tissues. MSCs show promise for cellular therapy for several disorders such as those associated with inflammation. In adults, MSCs primarily reside in the bone marrow (BM) and adipose tissues. In BM, MSCs are found at low frequency around blood vessels and trabecula. MSCs are attractive candidates for regenerative medicine given their ease in harvesting and expansion and their unique ability to bypass the immune system in an allogeneic host. Additionally, MSCs exert pathotropism by their ability to migrate to diseased regions. Despite the "attractive" properties of MSCs, their translation to patients requires indepth research. "Off-the-shelf" MSCs are proposed for use in an allogeneic host. Thus, the transplanted MSCs, when placed in a foreign host, could receive cue from the microenvironment for cellular transformation. An important problem with the use of MSCs involves their ability to facilitate the support of breast and other cancers as carcinoma-associated fibroblasts. MSCs could show distinct effect on each subset of cancer cells. This could lead to untoward effect during MSC therapy since the MSCs would be able to interact with undiagnosed cancer cells, which might be in a dormant state. Based on these arguments, further preclinical research is needed to ensure patient safety with MSC therapy. Here, we discuss the basic biology of MSCs, discuss current applications, and provide evidence why it is important to understand MSC biology in the context of diseased microenvironment for safe application.