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Evaluation of HSPD1 (Heat Shock Protein, 60) as a theranostic target for breast cancer

HSPD1（热休克蛋白，60）作为乳腺癌治疗靶点的评估

基本信息

批准号：
10653869
负责人：
Deepa Bedi
金额：
$ 36.75万
依托单位：
TUSKEGEE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-20 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10653869
关键词：
Accounting Affinity Apoptotic Bacteriophages Binding Bioinformatics Breast Breast Cancer Cell Breast Cancer Patient Breast cancer metastasis Cause of Death Cells Chaperonin 60 Complex Data Set Development Diagnosis Diagnostic Disease Disease Progression Distant Drug Delivery Systems Drug Targeting Epithelium Evaluation Event Fibroblasts Funding Goals Heat shock proteins In Vitro Indolent Invaded Laboratories Ligands Malignant Neoplasms Mesenchymal Metastatic breast cancer Mitochondria Morphology Neoplasm Metastasis Oncogenes Oncogenic Organ Organ failure Outcome Study Patients Peptides Phage Display Phenotype Prognosis Property Proteins Research Role Site Specificity Survival Rate System Techniques Technology Therapeutic Therapeutic Agents Time Tissues Up-Regulation Western Blotting Woman aggressive breast cancer breast cancer progression breast cancer survival cancer cell clinical biomarkers clinical decision-making clinically relevant epithelial to mesenchymal transition imaging agent improved in vivo insight malignant breast neoplasm mammary epithelium migration novel peptidomimetics prognostic protein aminoacid sequence receptor targeted biomarker theranostics tumor tumor growth

项目摘要

Our laboratory has used a novel subtractive phage display technique to identify phage ligands that can specifically and selectively bind to epithelial to mesenchymal transitioned (EMT) breast cancer cells. We selected and characterized several phages that had affinity to EMT cells. One of the phages with the foreign peptide sequence CLGLRGSLC bound with greater affinity and specificity to EMT breast cancer and EMT fibroblasts cells. We identified HSPD1 (heat shock protein, 60Kda) as a putative binding partner to CLGLRGSLC phage. Subsequent studies, including bioinformatics dataset analysis, immunoblotting of indolent vs aggressive breast cancer cells, immunohistochemical analysis of primary and metastatic breast cancer tissues showed increased expression of HSPD1 during disease progression and correlates with survival of breast cancer patients. This preliminary engenders the novel hypothesis that HSPD1 might play a role in metastatic progression of breast cancer and the discovery of HSPD1-binding peptide also suggests the use of novel imaging and therapeutic agents based on the selective binding. We hypothesize that HSPD1 is a novel oncogene that can serve as a clinically relevant marker for breast cancer metastasis and an ideal receptor that can be utilized for tumor-targeted drug delivery to metastatic sites. Following specific aims will be pursued: a) to determine if HSPD1 expression correlates with metastatic disease. b) to determine the oncogenic role of HSPD1 in breast cancer development and progression invitro and invivo, c) will aim to develop peptidomimetic targeting system to suppress metastasis based on HSPD1-binding phage peptide fused to proapoptotic moiety D(KLAKLAK)2.

我们的实验室使用了一种新的减法噬菌体展示技术来鉴定噬菌体

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nanobody-based CTLA4 inhibitors for immune checkpoint blockade therapy of canine cancer patients.

DOI：
10.1038/s41598-021-00325-3
发表时间：
2021-10-21
期刊：
Scientific reports
影响因子：
4.6
作者：
Marable J;Ruiz D;Jaiswal AK;Bhattacharya R;Pantazes R;Agarwal P;Suryawanshi AS;Bedi D;Mishra A;Smith BF;Sandey M
通讯作者：
Sandey M

Characterization of Canine Adenovirus Type 2 Virus Infection Pattern in Canine and Human Cell Lines.

DOI：
10.1155/2022/3658970
发表时间：
2022
期刊：
ADVANCES IN VIROLOGY
影响因子：
2.2
作者：
Hogans, Madison D.;Kretzschmar, Will P.;Higgins, Theresa A.;Chakrabortty, Atonu;Nance, Rebecca L.;Smith, Bruce F.;Bedi, Deepa;Sandey, Maninder;Agarwal, Payal
通讯作者：
Agarwal, Payal

Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells.