Role of a novel angiogenic factor, YKL-40, in breast cancer progression

新型血管生成因子 YKL-40 在乳腺癌进展中的作用

• 批准号: 7465050
• 负责人: RONG SHAO
• 金额: $ 23.38万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7465050
• 关键词: Address; Advanced Malignant Neoplasm; Angiogenic Factor; Animal Model; Animals; Binding; Biochemical; Biological Markers; Biological Process; Blood; Blood Vessels; Breast; CHI3L1 gene; Cancer Patient; Cancerous; Cardiac; Cell Line; Cells; Chimeric Proteins; Chondrocytes; Chromatography; Colorectal; Cultured Cells; Data; Development; Diagnostic Neoplasm Staging; Disease; Disease-Free Survival; Disseminated Malignant Neoplasm; Distant Metastasis; Endothelial Cells; Exhibits; Fatty acid glycerol esters; Heparin Binding; Human; Image; Immunocompromised Host; In Vitro; Injection of therapeutic agent; Invaded; Lead; Malignant Neoplasms; Malignant neoplasm of ovary; Mammary gland; Measures; Modeling; Molecular; Mus; Myeloid Leukemia; Neoplasm Metastasis; Patients; Play; Process; Proliferating; Proteins; Public Health; Research; Research Personnel; Role; Role playing therapy; SCID Beige Mouse; Sampling; Serum; Site; Smooth Muscle Myocytes; Source; Specimen; Surveys; System; Testing; Therapeutic Intervention; Tissue Banks; Tissues; Tumor Angiogenesis; Vascular Endothelial Cell; Vascular blood supply; Vascularization; Xenograft procedure; angiogenesis; arginyllysine; bone; cancer cell; cancer diagnosis; density; human tissue; in vitro Assay; in vivo; insight; macrophage; malignant breast neoplasm; mutant; neoplastic cell; novel; outcome forecast; prognostic; response; syndecan; tumor; tumor growth; tumor progression; tumor xenograft; vector control

DESCRIPTION (provided by applicant): A protein called YKL-40 is elevated in the blood serum of patients with breast, colorectal, and ovarian cancer, as well as myeloid leukemia. These patients with high YKL-40 serum levels have a poor prognosis and short survival, meaning that YKL-40 levels might offer a way to measure the progression of multiple cancers. As yet, researchers do not understand the role YKL-40 plays in cancer progression. Our preliminary data suggest that YKL-40 might cause new blood vessels to form in tumors, thereby facilitating their ability to invade and metastasize. In order for cancerous tumors to progress and metastasize they require the formation of new blood vessels, a process termed angiogenesis. These vessels carry blood to tumors at both the primary and secondary sites, allowing the cancerous cells to proliferate and expand. Without this nourishing blood supply, the cells die. Therefore, angiogenesis is a tantalizing target for therapeutic intervention. We hypothesize that YKL-40 is produced by cancer cells to promote angiogenesis in vascular endothelial cells, which are the cells lining small blood vessels. This enhanced angiogenesis facilitates tumor growth, invasion, and metastasis. To test this hypothesis, we will pursue three specific aims: 1) to identify correlations between YKL-40 level and markers of progression in human breast cancer; 2) to determine molecular mechanisms underlying YKL-40-induced tumor angiogenesis and progression; and 3) to examine the effects of YKL-40 on tumor angiogenesis and metastasis in xenograft tumor models. We will utilize our extensive human tissue bank to analyze cancer samples to determine if there is a correlation between the amount of YKL-40 and cancer stage, cancer survival, and blood vessel density. We will use molecular studies to determine the mechanisms used by YKL-40 to direct a cell to form blood vessels. Finally, we will use cultured cells and animal models to directly observe the effects of YKL-40 on tumor growth, invasion, and metastasis. PUBLIC HEALTH RELEVANCE: Our research may well lead to testing for YKL-40 levels in cancer diagnosis and prognosis. It may also point to YKL-40 as a target for therapeutic intervention in advanced cancers that have thus far proved difficult to treat.

描述（由申请人提供）：一种称为YKL-40的蛋白质在乳腺癌，结直肠癌和卵巢癌以及髓样白血病患者的血清中升高。 这些YKL-40血清水平高的患者预后较差，生存率短，这意味着YKL-40水平可能提供了一种测量多种癌症进展的方法。 迄今为止，研究人员还不了解YKL-40在癌症进展中的作用。 我们的初步数据表明，YKL-40可能会导致新血管形成肿瘤，从而促进它们侵入和转移的能力。 为了使癌性肿瘤进展和转移，它们需要形成新的血管，这是一种称为血管生成的过程。 这些血管在原发性和次要部位都将血液带到肿瘤，从而使癌细胞扩散并扩展。 没有这种滋养血液供应，细胞会死亡。 因此，血管生成是治疗干预的诱人靶标。 我们假设YKL-40是由癌细胞产生的，以促进血管内皮细胞的血管生成，这些细胞是小血管内衬的细胞。 这种增强的血管生成促进了肿瘤的生长，侵袭和转移。 为了检验这一假设，我们将追求三个特定的目的：1）确定人类乳腺癌中YKL-40水平和进展标志的相关性； 2）确定YKL-40诱导的肿瘤血管生成和进展的分子机制； 3）检查YKL-40对异种移植肿瘤模型中肿瘤血管生成和转移的影响。 我们将利用广泛的人体组织库来分析癌症样品，以确定YKL-40的量与癌症阶段，癌症生存和血管密度之间是否存在相关性。 我们将使用分子研究来确定YKL-40用于指导细胞形成血管的机制。 最后，我们将使用培养的细胞和动物模型直接观察YKL-40对肿瘤生长，侵袭和转移的影响。 公共卫生相关性：我们的研究很可能导致在癌症诊断和预后中测试YKL-40水平。这也可能指出YKL-40是对迄今为止难以治疗的高级癌症治疗干预的靶标。