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Methods and Reagents for Determination and Treatment of Organotropic Metastasis

詳細技術說明
This invention provides methods and reagents to predict potential and sites of metastasis in a cancer patient and methods and reagents to prevent or treat metastasis with integrin inhibitors or inhibitors of the activated S100 molecules.
*Abstract

TechnologyOverview

Stephen Paget first proposed the “seed-and-soil”hypothesis in 1889 that organ distribution of metastases is a non-randomevent. Experimental metastasis assaysprovided support for Paget’s organ-specific metastasis theory, but a deeperunderstanding of the molecular basis of organ-specific metastasis is essentialfor prognosing metastasis and provided potential therapeutics.

Exosomesare small membrane vesicles containing functional biomolecules. Cornell researchers demonstrated thatmolecules present on tumor-derived exosome are “addressing” them to specificorgans. The researchers revealed thatdistinct integrin expression patterns are associated with organotropicmetastasis: exosomal integrins α6β4 and α6β1are associated with lung metastasis while exosomal integrin αvβ5is linked to liver metastasis (Fig. 1). The researchers confirmed thesefindings by exosome proteomics for 28 organ-specific metastatic cell lines.

The researchers also showed thattumor-derived exosomes uptaken by organ-specific cells prepares thepre-metastatic niche and activates Src phosphorylation and pro-inflmmatory S100gene expression (Fig. 1). Targeting theintegrins decreases exosomal uptake, as well as lung and liver metastasis. Their clinical data also demonstrated thatexosomal integrins in cancer patient plasmas correlate with and predict likelysites of metastasis.

This study, published in Nature, provides potential biomarkersfor prognosing metastasis and also provides potential therapeutics for thetreatment and prevention of metastasis.

PotentialApplications

  • Predict potential and sites of metastasis with integrinexpression profiles in circulating plasma exosomes
  • Treat or prevent metastasis based on the integrin profileexpressed on the tumor derived exosomes with a therapeutic integrin inhibitor
  • Treat or prevent metastasis with inhibitors of S100molecules

Advantages

  • Easy and non-invasive prognosis - exosomal samples can be obtained noninvasively and repeatedly fromspecimens such as blood and urine
  • Metastasiscan be prevented or treated before the metastasis sites are established, whichis essential for patients’ survival
*Licensing
Brian J. Kelly, Directorbjk44@cornell.edu646-962-7045
其他

Tumourexosome integrins determine organotropic metastasis. Nature, 2015,doi:10.1038/nature15756.

國家/地區
美國

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