Direct evidence that PTHrP expression promotes prostate cancer progression in bone
Direct evidence that PTHrP expression promotes prostate cancer progression in bone
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DOI：
10.1016/j.bbrc.2004.11.162
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发表时间：
2005-02-11
影响因子：
3.1
通讯作者：
Geller, J
中科院分区：
文献类型：
--
作者：
Deftos, LJ;Barken, I;Geller, J
甲状旁腺相关蛋白（PTHrP）是一种在许多恶性肿瘤和正常组织中表达的癌蛋白。在基本上每个表达位点，PTHrP调节细胞生长和增殖。我们和其他研究者以前曾报道PTHrP在前列腺癌中广泛表达。对于这种肿瘤，有大量的体外和相关数据表明PTHrP表达调节肿瘤的进展，特别是在骨中，但很少有直接数据。我们研究了PTHrP表达对前列腺癌行为的影响，直接在小鼠模型的人前列腺癌细胞转染表达不同形式的多肽，然后intraskeletally注射。通过放射学和血清肿瘤标志物的测量来评估前列腺癌细胞的骨骼进展。PTHrP转染将非侵袭性细胞系转化为在骨骼中进展的细胞系：与未转染的细胞相比，注射PTHrP转染的细胞导致骨中更大的肿瘤进展，并且这种效果也受到PTHrP的非氨基末端肽的影响。PTHrP、IL-6、IL-8和钙的血清测量反映了肿瘤负荷。我们的实验提供了PTHrP表达导致前列腺癌细胞骨骼进展的直接体内证据。(C)2004爱思唯尔公司All rights reserved.
Parathyroid hormone-related protein (PTHrP) is an oncoprotein that is expressed in many malignancies as well as normal tissues. At essentially every site of expression, PTHrP regulates cell growth and proliferation. We and other investigators have previously reported that PTHrP is widely expressed by prostate cancer. For this tumor, there are substantial in vitro and correlative data that PTHrP expression regulates the progression of the tumor, especially in bone, but little direct data. We studied the effects of PTHrP expression on prostate cancer behavior directly in a mouse model of human prostate cancer cells that were transfected to express different forms of the polypeptide and then injected intraskeletally. Skeletal progression of the prostate cancer cells was evaluated radiologically and by measurement of serum tumor markers. PTHrP transfection converted a non-invasive cell line into one that progressed in the skeleton: Injection of the PTHrP transfected cells resulted in greater tumor progression in bone when compared to non-transfected cells, and this effect was also influenced by non-amino terminal peptides of PTHrP. Serum measurements of PTHrP, IL-6, IL-8, and calcium reflected tumor burden. Our experiments provide direct in vivo evidence that PTHrP expression results in the skeletal progression of prostate cancer cells. (C) 2004 Elsevier Inc. All rights reserved.