Mechanistic understanding of the lifecycle of a circulating hybrid cell.

对循环混合细胞生命周期的机制理解。

• 批准号: 10746344
• 负责人: Summer Lynne Gibbs
• 金额: $ 1.42万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10746344
• 关键词: Address; Behavioral; Binding Sites; Biological; Biology; Cells; Cessation of life; Circulation; Colorectal Cancer; Computer Analysis; Diagnosis; Disease; Disseminated Malignant Neoplasm; Distant; Evaluation; Hybrid Cells; Knowledge; Life Cycle Stages; Malignant Neoplasms; Micrometastasis; Neoplasm Metastasis; Patient Care; Patients; Phase; Phenotype; Population; Primary Neoplasm; Property; Proteins; Recurrent tumor; Technology; Therapeutic; Time; Tumor stage; cancer care; cohort; colon cancer patients; insight; metastatic process; multiple omics; neoplastic; neoplastic cell; novel therapeutic intervention; peripheral blood; treatment stratification; tumor; tumor initiation; tumor progression

Project Summary Metastatic disease accounts for >90% of cancer-related deaths worldwide, yet this phase of tumor progression is the least biologically understood. The consequence of this lack of knowledge is that we do not have the appropriate therapeutic arsenal to defeat metastatic cancer. New revelations for colorectal cancer point to shed neoplastic cells into peripheral blood even from early stage tumors, suggesting this is why some early stage tumors recur despite seemingly successful treatment. However, whether all early stage primary tumors shed neoplastic cells, or if only subsets of more aggressive neoplastic cells garner ability to disseminate is not known. This highlights the critical gap in knowledge of the mechanisms underlying neoplastic cell dissemination leading to distant disease. Identifying the key features within the lifecycle of a disseminated tumor cell will unravel this important step in tumor progression with potential to influence management of cancer care. Our study leverages newly developed state-of-the-art phenotypic analyses of key attributes of a recently discovered neoplastic hybrid cell in primary tumors and in peripheral blood, termed circulating hybrid cells (CHCs), supported by cutting-edge computational analyses. Interestingly, CHCs harbor tumor-initiating properties implying that they have high potential as effectors of metastatic tumor seeding. We will detail cells poised to disseminate from the primary tumor into circulation and seed metastatic sites combining protein, multi-omic analyses and functional behavioral analyses. A focus on a stage II and late stage colorectal cancer cohorts support analyses across the disease axis, with an emphasis on stage II CRC patients with undetected micrometastases at the time of diagnoses. Evaluation of the lifecycle of the hybrid cell from primary tumor to dissemination will provide biologic insight into the metastatic process with great potential to impact the management and care of patients with cancer.

项目摘要 转移性疾病占全球癌症相关死亡的90%以上，但肿瘤进展的这一阶段 是生物学上最不了解的。这种知识缺乏的后果是，我们没有 适当的治疗武器来击败转移性癌症。结直肠癌的新发现表明， 肿瘤细胞进入外周血，即使是从早期肿瘤，这表明这就是为什么一些早期肿瘤， 尽管治疗看似成功，但肿瘤复发。然而，是否所有的早期原发性肿瘤脱落 肿瘤细胞，或者是否只有更具侵袭性的肿瘤细胞的亚群获得扩散能力尚不清楚。 这突出了在肿瘤细胞播散的基础机制的知识的关键差距，导致肿瘤细胞的扩散。 遥远的疾病确定播散性肿瘤细胞生命周期内的关键特征将解开这一难题 肿瘤进展的重要步骤，有可能影响癌症护理管理。我们的研究 对最近发现的肿瘤性杂交瘤的关键属性进行了最新开发的最先进的表型分析 在原发性肿瘤和外周血中的细胞，称为循环杂交细胞（CHC），由尖端的 计算分析。有趣的是，CHC具有肿瘤起始特性，这意味着它们具有高的肿瘤发生率。 作为转移性肿瘤种植效应物的潜力。我们将详细介绍准备从原发灶扩散的细胞 结合蛋白质、多组学分析和功能行为分析， 分析。对II期和晚期结直肠癌队列的关注支持了对整个疾病的分析 轴，重点是诊断时未检测到微转移的II期CRC患者。 对杂交细胞从原发性肿瘤到播散的生命周期的评估将为以下方面提供生物学见解： 转移过程具有很大的潜力，影响癌症患者的管理和护理。