the PHSCN Sequence in Prostate Carcinoma Anti-invasive , Antitumorigenic , and Antimetastatic Activities of Updated Version
the PHSCN Sequence in Prostate Carcinoma Anti-invasive , Antitumorigenic , and Antimetastatic Activities of Updated Version
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发表时间：
2000
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通讯作者：
D. Livant;R. K. Brabec;K. Pienta;David L. Allen;K. Kurachi;S. Markwart;Ameet Upadhyaya
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作者：
D. Livant;R. K. Brabec;K. Pienta;David L. Allen;K. Kurachi;S. Markwart;Ameet Upadhyaya
使用天然无血清SU-ECM基底膜作为侵袭底物表明，血浆纤连蛋白是刺激DU 145人和转移性MATLyLu（MLL）大鼠前列腺癌细胞侵袭所必需的。这种活性映射到PHSRN序列，其诱导侵袭性整合素α 5 b1。竞争性抑制剂PHSCN能阻断PHSRN和血清诱导的侵袭。乙酰化、酰胺化的PHSCN（Ac-PHSCN-NH 2）的效力高30倍;然而，AcHSPNC-NH 2无活性。接受皮下注射的大鼠通过静脉内注射1 mg Ac-PHSCN-NH 2或Ac-HSPNC-NH 2，每周三次，仅在手术切除大的（2cm）MLL肿瘤后开始静脉内注射1 mg Ac-PHSCN-NH 2，每周三次，全身处理100，000个MLL细胞，或不进行处理。MLL肿瘤在Ac-HSPNC-NH 2处理的和未处理的大鼠中快速生长。在MLL细胞注射后1天开始用Ac-PHSCN-NH 2治疗的大鼠中，MLL肿瘤生长在治疗的前16天期间减少了99.9%，尽管随后发生了肿瘤生长。用抗PECAM-1免疫染色的MLL肿瘤冷冻切片显示，AcPHSCN-NH 2在此期间抑制新生血管形成12倍。无论是在MLL细胞注射后开始还是仅在MLL肿瘤切除后开始，Ac-PHSCN-NH 2治疗使MLL肺集落和微转移的数量减少40至>100倍，而Ac-HSPNCNH 2无活性。因此，Ac-PHSCN-NH 2可能是一种有效的抗肿瘤和抗转移剂，用于广泛转移前的手术后使用。
Using naturally serum-free SU-ECM basement membranes as invasion substrates showed that plasma fibronectin was necessary to stimulate invasion by DU 145 human and metastatic MATLyLu (MLL) rat prostate carcinoma cells. This activity mapped to the PHSRN sequence, which induced invasion througha5b1 integrin. PHSCN, a competitive inhibitor, blocked both PHSRNand serum-induced invasion. Acetylated, amidated PHSCN (Ac-PHSCN-NH2) was 30-fold more potent; however, AcHSPNC-NH2 was inactive. Rats receiving injections s.c. with 100,000 MLL cells were treated systemically by i.v. injection three times weekly with 1 mg of either Ac-PHSCN-NH2 or Ac-HSPNC-NH2 beginning 24 h later, three times weekly with 1 mg of Ac-PHSCN-NH2 beginning only after surgery to remove large (2 cm) MLL tumors, or were left untreated. MLL tumors grew rapidly in Ac-HSPNC-NH2-treated and in untreated rats. MLL tumor growth in rats treated with Ac-PHSCN-NH 2 beginning 1 day after MLL cell injection was reduced by 99.9% during the first 16 days of treatment, although subsequent tumor growth occurred. MLL tumor cryosections immunostained with anti-PECAM-1 showed that AcPHSCN-NH2 inhibited neovascularization by 12-fold during this time. Whether initiated after MLL cell injection or only after MLL tumor removal, Ac-PHSCN-NH2 treatment reduced the numbers of MLL lung colonies and micrometastases by 40to >100-fold, whereas Ac-HSPNCNH2 was inactive. Thus, Ac-PHSCN-NH2 may be a potent antitumorigenic and antimetastatic agent for postsurgical use prior to extensive metastasis.