Extracellular PTEN-long Polypeptide for Solid Tumor Treatment
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Solution Overview
Problem
Current understanding of PTEN protein localization and function is limited, as it is primarily considered cytoplasmic or nuclear, with no evidence of extracellular presence, which hinders the development of effective therapeutic strategies for solid tumors.
Innovation Solution
Identification and characterization of a novel protein, PTEN-long, which contains an N-terminal signal peptide and is secreted extracellularly, offering a new avenue for treating solid tumors through administration of its polypeptide or expression vector to inhibit tumor growth, induce apoptosis, and inhibit angiogenesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If PTEN is considered only cytoplasmic or nuclear, then the understanding of PTEN localization is simple, but therapeutic strategies for solid tumors are limited
Solution Approach 1:
The patent identifies and characterizes a novel extracellular form of PTEN (PTEN-long) that is distinct from the previously known cytoplasmic and nuclear forms. This segmentation of PTEN into multiple localization forms (cytoplasmic, nuclear, and extracellular) provides more complete information about PTEN distribution, enabling development of targeted therapeutic strategies for solid tumors by exploiting the extracellular localization.
2Adaptability or versatility
If PTEN-long with N-terminal signal peptide is identified, then extracellular secretion capability is achieved, but protein structure complexity increases
Solution Approach 1:
The patent focuses on extracting and characterizing the N-terminal signal peptide sequence from PTEN-long that confers extracellular secretion capability. By identifying this specific functional element, the invention separates the secretion function from the rest of the PTEN structure, allowing for potential modular applications where the signal peptide can be used to redirect PTEN or PTEN-like proteins to extracellular locations without requiring complete structural redesign.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
PTEN-long effectively treats solid tumors by inhibiting growth, inducing apoptosis in vascular epithelial cells, and reducing angiogenesis, demonstrating anti-tumor and anti-angiogenic activity, with potential applications in various cancer types.
Implementation Method 1
The PTEN tumor suppressor is a cytoplasmic phosphatase which dephosphorylates the important second messenger phosphatidylinositol 3,4,5-triphosphate
Implementation Method 2
PTEN-long, which contains an N-terminal signal peptide and which is secreted extracellularly
Data Source
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AI summary
An isolated human phosphatase and tensin homolog long polypeptide (PTEN-long) comprising SEQ ID NO:1, fragments and analogs thereof, nucleic acids encoding such and compositions comprising such are provided. Methods to inhibit angiogenesis in a solid tumor, treat a solid tumor, and inhibit growth of a solid tumor using PTEN-long, fragments and analogs thereof, are provided.