Midkine

[5] Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK).

A molecular complex containing receptor-type tyrosine phosphatase zeta (PTPζ), low density lipoprotein receptor-related protein (LRP1), anaplastic leukemia kinase (ALK) and syndecans is considered to be its receptor.

[7] The expression of MK (mRNA and protein expression) has been found to be elevated in multiple cancer types, such as neuroblastoma, glioblastoma, Wilms' tumors, thyroid papillary carcinomas,[7] colorectal, liver, ovary, bladder, breast, lung, esophageal, stomach, and prostate cancers.

In some cases, these elevated levels of MK also indicate a poorer prognosis of the disease, such as in neuroblastoma, glioblastoma, and bladder carcinomas.

[10][11] The resistance to chemotherapy seems to be reversible by administering chemo-resensitization drugs, such as verapamil,[12] which acts not via MK alteration, but by inhibiting the P-glycoprotein pump that exports cytotoxins out of cells.

[10] In addition, the mechanism for such anti-apoptotic (anti-cell death) activity was studied, specifically using the chemotherapeutic Doxorubicin (Adriamycin) on osteosarcoma (Saos2) cells.

[14] Miyakawa et al. have successfully established the method to prepare the MDK specific RNA aptamers[15] by the use of the recombinant midkine[16] and pleiotrophin.