Spellman J E, Kulesz-Martin M F, Blumenson L E, Beckett M A, Weichselbaum R R
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263.
J Surg Res. 1995 Feb;58(2):165-74. doi: 10.1006/jsre.1995.1026.
F.2a and B.2, cell clones of the human squamous cell carcinoma SCC-12, were examined to characterize their interactions through the expression of growth factors. F.2a was nontumorigenic yet B.2 was fully tumorigenic when injected into the flanks of athymic nude mice. Combination injections of F.2a and a subtumorigenic level of B.2 produced tumors. F.2a and B.2 overexpressed the 4.8-kb transcript for transforming growth factor-alpha (TGF-alpha) as well as the 10.5- and 5.8- kb transcripts for the epidermal growth factor receptor. Neither clone expressed the transcript for epidermal growth factor, while both expressed transcripts for insulin-like growth factor-I (IGF-I) of 8.15, 4.9, and 1.6 kb and transcripts for its receptor of 8.5 and 6.5 kb. Conditioned medium (CM) from either clone stimulated the growth of itself and the other clone in tissue culture. Both clones produced intracellular TGF-alpha detectable by immunohistochemical staining, but not detectable in CM by enzyme-linked immunosorption assay. IGF-I was detected at low levels in CM by radioimmunoassay. Neutralizing antibodies to TGF-alpha but not IGF-I partially inhibit the growth of both clones in tissue culture. These results suggest that (1) TGF-alpha is active in autocrine signaling (2) IGF-I is not directly stimulatory, and (3) additional factors, as yet unidentified, are present in CM and enhance tumor growth. It is concluded that human squamous cell carcinoma SCC-12 is composed of tumorigenic and nontumorigenic clones which interact to enhance growth.
对人鳞状细胞癌SCC - 12的细胞克隆F.2a和B.2进行了检测，以通过生长因子的表达来表征它们之间的相互作用。将F.2a注射到无胸腺裸鼠的侧腹时不具有致瘤性，而B.2具有完全致瘤性。联合注射F.2a和亚致瘤水平的B.2会产生肿瘤。F.2a和B.2均过度表达转化生长因子 - α（TGF - α）的4.8 kb转录本以及表皮生长因子受体的10.5 kb和5.8 kb转录本。两个克隆均未表达表皮生长因子的转录本，而两者都表达了8.15、4.9和1.6 kb的胰岛素样生长因子 - I（IGF - I）转录本及其8.5和6.5 kb的受体转录本。来自任一克隆的条件培养基（CM）在组织培养中刺激自身和另一克隆的生长。两个克隆均产生可通过免疫组织化学染色检测到的细胞内TGF - α，但通过酶联免疫吸附测定在CM中未检测到。通过放射免疫测定在CM中检测到低水平的IGF - I。针对TGF - α而非IGF - I的中和抗体部分抑制了两个克隆在组织培养中的生长。这些结果表明：（1）TGF - α在自分泌信号传导中起作用；（2）IGF - I不具有直接刺激作用；（3）CM中存在尚未鉴定的其他因子，可促进肿瘤生长。结论是人鳞状细胞癌SCC - 12由相互作用以促进生长的致瘤性和非致瘤性克隆组成。
