Metastasis specific splice variants of mena and uses thereof in diagnosis, prognosis and treatment of tumors
View Patent ↗Methods and kits for diagnosis, prognosis and treatment of metastatic tumors are provided where the metastatic tumor is characterized by changes in expression of +++, ++ and/or 11a variants of Mena.
1. A method for determining whether a subject has a metastatic tumor comprising assaying a blood, tissue and/or tumor sample of the subject for expression of the ++ and/or +++ and 11a variants of Mena, wherein expression of the ++ and/or +++ variant of Mena is compared to expression of Mena 11a and wherein overexpression of the ++ and/or +++ variant of Mena compared to expression of Mena 11a indicates the presence of a metastatic tumor.
2. The method of claim 1 , wherein the tumor is a secretory epithelial tumor.
3. The method of claim 1 , wherein the tumor is a breast, pancreas, prostate, colon, brain, liver, lung, head or neck tumor.
4. The method of claim 1 , wherein the sample is assayed using an agent that specifically binds to the ++ isoform (SEQ ID NO:2) or +++ isoform (SEQ ID NO:4) of Mena or to nucleic acid encoding the ++ isoform or +++ isoform of Mena.
5. The method of claim 4 , wherein the agent is an antibody, a peptide or an aptamer.
6. The method of claim 4 , wherein the agent is labeled with a detectable marker.
7. The method of claim 1 , wherein the sample is assayed for the ++ variant of Mena.
8. The method of claim 1 , wherein the sample is assayed for the +++ variant of Mena.
9. The method of claim 1 , wherein the sample is assayed for both the ++ variant and the +++ variant of Mena.
10. The method of claim 1 , wherein overexpression of the ++ and/or +++ variant of Mena occurs in combination with overexpression of one or more of Arp 2/3 complex subunit p21, Arp 2/3 complex subunit p16, actinin alpha 3, capping protein alpha 1, epidermal growth factor receptor (EGFR), WAVE 3, actin gamma, LIM-kinase 1, cofilin 1, Rock 1, RhoA or protein kinase Cz.
11. The method of claim 1 , wherein overexpression of the ++ and/or +++ variants and decreased expression of the 11a variant of Mena, together, indicate the presence of a metastatic tumor.
12. The method of claim 1 , wherein the sample is assayed using an agent that specifically binds to Mena 11a (SEQ ID NO:24) or to nucleic acid encoding Mena 11a.
13. A method for assessing the efficacy of therapy to treat a metastatic tumor in a subject who has undergone or is undergoing treatment for a metastatic tumor, the method comprising assaying a blood, tissue and/or tumor sample of the subject for expression of the ++ and/or +++ and 11a variants of Mena, wherein expression of the ++ and/or +++ variant of Mena is compared to expression of Mena 11a and wherein overexpression of the ++ and/or +++ variant of Mena compared to expression of Mena 11a is indicative of a need to continue therapy to treat the tumor.
14. The method of claim 13 , wherein overexpression of the ++ and/or +++ variants and decrease in expression of the 11a variant of Mena is indicative of a need to continue therapy to treat the tumor.
15. The method of claim 13 , wherein the tumor is a secretory epithelial tumor.
16. The method of claim 13 , wherein the tumor is a breast, pancreas, prostate, colon, brain, liver, lung, head or neck tumor.
17. The method of claim 13 , wherein the sample is assayed for the ++ variant of Mena.
18. The method of claim 13 , wherein the sample is assayed for the +++ variant of Mena.
19. The method of claim 13 , wherein the sample is assayed for both the ++ variant and the +++ variant of Mena.
20. The method of claim 13 , wherein the sample is assayed using an agent that specifically binds to the ++ isoform (SEQ ID NO:2) or +++ isoform (SEQ ID NO:4) of Mena or to nucleic acid encoding the ++ isoform or +++ isoform of Mena.
21. The method of claim 20 , wherein the agent is an antibody, a peptide or an aptamer.
22. The method of claim 20 , wherein the agent is labeled with a detectable marker.
23. The method of claim 13 , wherein the sample is assayed using an agent that specifically binds to Mena 11a (SEQ ID NO:24) or to nucleic acid encoding Mena 11a.
24. A method for assessing the prognosis of a subject who has a metastatic tumor, comprising assaying a blood, tissue and/or tumor sample of the subject for expression of the ++ and/or +++ and 11a variants of Mena, wherein expression of the ++ and/or +++ variant of Mena is compared to expression of Mena 11a and wherein the subject's prognosis improves with a decrease in expression of the ++ and/or +++ variant of Mena compared to expression of Mena 11a.
25. The method of claim 24 , wherein the subject's prognosis improves with a decrease in expression of the ++ and/or +++ variants of Mena and an increase in expression of the 11a variant of Mena.
26. The method of claim 24 , wherein the tumor is a secretory epithelial tumor.
27. The method of claim 24 , wherein the tumor is a breast, pancreas, prostate, colon, brain, liver, lung, head or neck tumor.
28. The method of claim 24 , wherein the sample is assayed for the ++ variant of Mena.
29. The method of claim 24 , wherein the sample is assayed for the +++ variant of Mena.
30. The method of claim 24 , wherein the sample is assayed for both the ++ variant and the +++ variant of Mena.
31. The method of claim 24 , wherein the sample is assayed using an agent that specifically binds to the ++ isoform (SEQ ID NO:2) or +++ isoform (SEQ ID NO:4) of Mena or to nucleic acid encoding the ++ isoform or +++ isoform of Mena.
32. The method of claim 31 , wherein the agent is an antibody, a peptide or an aptamer.
33. The method of claim 31 , wherein the agent is labeled with a detectable marker.
34. The method of claim 24 , wherein the sample is assayed using an agent that specifically binds to Mena 11a (SEQ ID NO:24) or to nucleic acid encoding Mena 11a.