Anti-TESK2 (aa 329-571) polyclonal antibody

Brain metastases (BM) result from the spread of primary tumors to the brain and are a leading cause of cancer mortality in adults. Secondary tissue colonization remains the main bottleneck in metastatic development, yet this "premetastatic" stage of the metastatic cascade, when primary tumor cells cross the blood-brain barrier and seed the brain before initiating a secondary tumor, remains poorly characterized. Current studies rely on specimens from fully developed macrometastases to identify therapeutic options in cancer treatment, overlooking the potentially more treatable "premetastatic" phase when colonizing cancer cells could be targeted before they initiate the secondary brain tumor. Here we use our established brain metastasis initiating cell (BMIC) models and gene expression analyses to characterize premetastasis in human lung-to-BM. Premetastatic BMIC engaged invasive and epithelial developmental mechanisms while simultaneously impeding proliferation and apoptosis. We identified the dopamine agonist apomorphine to be a potential premetastasis-targeting drug. In vivo treatment with apomorphine prevented BM formation, potentially by targeting premetastasis-associated genes KIF16B, SEPW1, and TESK2. Low expression of these genes was associated with poor survival of patients with lung adenocarcinoma. These results illuminate the cellular and molecular dynamics of premetastasis, which is subclinical and currently impossible to identify or interrogate in human patients with BM. These data present several novel therapeutic targets and associated pathways to prevent BM initiation. Significance: These findings unveil molecular features of the premetastatic stage of lung-to-brain metastases and offer a potential therapeutic strategy to prevent brain metastases. (C) 2018 AACR.

In this study we present the cDNA sequence of a novel putative protein kinase, denoted TESK2. The open reading frame of TESK2 encodes a putative 555-amino-acid protein, including a protein kinase consensus sequence in the N-terminal half. The protein kinase domain of TESK2 is structurally similar to the kinase domain of the protein serine/threonine kinase TESK1 (64% identity) and to those of the LIMK1 and LIMK2 kinases (42 and 39% identity, respectively). TESK2, together with TESK1, constitutes a second subgroup of the LIMK/TESK family of protein kinases, as revealed by phylogenetic analysis of the protein kinase domains. Chromosomal localization of human TESK2 was assigned to 1p32. Expression analysis of human TESK2 revealed a single mRNA species of 3.0 kb predominantly expressed in testis and prostate and low expression in most other tissues examined. Rat testicles expressed a single species of TESK2 mRNA of approximately 3.5 kb. However, the transcript was first detectable in rat testis after day 30 of postnatal development and was predominantly expressed in round spermatids. These observations suggest that TESK2 plays an important role in spermatogenesis. (C) 1999 Academic Press.