TMEM ACTIVE TEST AND USES THEREOF IN DIAGNOSIS, PROGNOSIS AND TREATMENT OF TUMORS
Disclosed are kits and methods for detecting the presence of tumor sites that are active in tumor cell dissemination and uses thereof for determining the risk of tumor cells undergoing hematogenous metastasis, for assessing the prognosis of a subject undergoing treatment for a localized tumor, for determining a course of treatment for a localized tumor, and for identifying agents to treat or prevent hematogenous metastasis.
1 - 3 . (canceled)
4 . A method for identifying an agent to treat or prevent hematogenous metastasis, the method comprising:
(a) contacting a tumor sample with the agent;
(b) assaying the tumor sample for the presence of TMEM Active sites by a method comprising performing an assay of the tumor sample to detect the presence of a macrophage and an endothelial cell, wherein the macrophage is detected by assaying for the presence of CD68 and the endothelial cell is detected by assaying for the presence of CD31; and performing an assay to detect the levels of Tie2 and VEGFA in the macrophage and at least one of VE-Cadherin and ZO-1 in the endothelial cell, wherein Tie2 H1 /VEGFA Hi macrophages having elevated levels of VEGFA relative to adjacent endothelial cells and tumor tissue, and endothelial cells having low levels of at least one of VE-Cadherin and ZO-1 indicate the presence of a TMEM Active site; and
(c) analyzing whether or not the agent reduces the number of TMEM Active sites, wherein an agent that reduces the number of TMEM Active sites is a candidate agent for treating or preventing hematogenous metastasis.
5 . The method of claim 4 , wherein the tumor is a breast, pancreas, prostate, colon, brain, liver, lung, head or neck tumor.
6 . The method of claim 4 , wherein the tumor is a breast tumor.