Melanoma and the Nervous System – Novel Pathways Mediated by Neurotrophins and Their Receptors

Pincelli, Carlo; Dallaglio, Katiuscia; Truzzi, Francesca

doi:10.5772/22053

Cited by 1 publication

(1 citation statement)

References 121 publications

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“…It weakly synergizes with the natural TrkC neurotrophin ligand NT3, enhancing cell survival but not differentiation . Overexpression of TrkC receptors is associated with some forms of cancer (e.g., neuroblastoma, medulloblastoma, and breast cancer) and with melanoma, − the latter being particularly interesting because lesions near the tissue surface can be most effectively radiated by UV light. Conversely, compounds with the inverted side chain sequence, i.e., YI-YI, did not show this activity.…”

Section: Results and Discussionmentioning

confidence: 99%

Double-Targeting Using a TrkC Ligand Conjugated to Dipyrrometheneboron Difluoride (BODIPY) Based Photodynamic Therapy (PDT) Agent

Kamkaew

Burgess

2013

J. Med. Chem.

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A molecule 1 (IY-IY-PDT) was designed to contain a fragment (IY-IY) that targets the TrkC receptor, and a photosensitizer that acts as an agent for photodynamic therapy (PDT). Molecule 1 had sub-micromolar photocytotoxicities to cells that were either engineered to stably express TrkC (NIH3T3-TrkC) or that naturally express high levels of TrkC (SY5Y neuroblastoma lines). Control experiments showed 1 is not cytotoxic in the dark, and has significantly less photocytotoxicity towards cells that do not express TrkC (NIH3T3-WT). Other controls featuring a similar agent 2 (YI-YI-PDT) which is identical and isomeric with 1 except that the targeting region is scrambled (a YI-YI motif, see text) showed 1 is considerably more photocytotoxic than 2 on TrkC+ cells. Imaging live TrkC+ cells after treatment with a fluorescent agent 1 (IY-IY-PDT) proved that 1 permeates into TrkC+ cells and localizes in the lysosomes. This observation indirectly indicates agent 1 enters the cells via the TrkC receptor. Consistent with this, the dose-dependent PDT effects of 1 can be competitively reduced by the natural TrkC ligand, neurotrophin NT3.

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