Tsujimoto H, Takhashi T, Hagiwara A, Shimotsuma M, Sakakura C, Osaki K, Sasaki S, Shirasu M, Sakakibara T, Ohyama T
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Br J Cancer. 1995 Mar;71(3):468-72. doi: 10.1038/bjc.1995.95.
To investigate the site-specific implantation of cancer cells in peritoneal dissemination, we inoculated CDF1 mice intraperitoneally with mouse P388 leukaemia cells labelled with bromodeoxyuridine (BrdU) and then observed immunohistochemically the distribution of the cells in the greater omentum taken from the mice using an anti-BrdU antibody. We found the BrdU-labelled cells infiltrating selectively into the milky spots in the omentum. Furthermore, we intraperitoneally inoculated the BrdU-labelled P388 cells at 10(5), 10(6) and 10(7) cells per mouse into three groups of ten CDF1 mice and then quantified the distribution of the BrdU-labelled cells by counting the number of the labelled cells per unit area at each milky spot and non-milky spot site in the omentum. Inoculations of 10(5), 10(6) and 10(7) BrdU-labelled P388 cells per mouse resulted in 15.8 +/- 13.3, 120 +/- 46.5 and 504 +/- 208 cells mm-2 respectively in the milky spot sites and 9.14 x 10(-3) +/- 1.58 x 10(-2), 1.14 x 10(-1) +/- 7.82 x 10(-2) and 7.07 x 10(-1) +/- 5.98 x 10(-1) cells mm-2 respectively in the non-milky spot sites. The ratios of the mean labelled cell numbers in the milky spot sites vs those in the non-milky spot sites were 1728:1, 1049:1 and 713:1 respectively. In all cases, there were statistically significant differences in the number of BrdU-labelled cells mm-2 between milky spot sites and non-milky spot sites. However, the ratios decreased as the numbers of inoculated cells increased. In addition, we inoculated C57/BL mice intraperitoneally with B-16 PC melanoma cells, which were easily differentiated from the other cells by the intrinsic black melanin, and examined the distribution of the cells macro- and microscopically. The B-16 PC melanoma cells were also found to be infiltrating preferentially into the milky spots in the omentum. These results suggest that cancer cells seeded intraperitoneally specifically infiltrate the milky spots in the early stages of peritoneal dissemination.
为了研究癌细胞在腹膜播散中的位点特异性植入,我们给CDF1小鼠腹腔内接种用溴脱氧尿苷(BrdU)标记的小鼠P388白血病细胞,然后使用抗BrdU抗体通过免疫组织化学方法观察取自这些小鼠的大网膜中细胞的分布。我们发现BrdU标记的细胞选择性地浸润到大网膜的乳斑中。此外,我们将每只小鼠分别接种10⁵、10⁶和10⁷个BrdU标记的P388细胞到三组每组十只CDF1小鼠的腹腔内,然后通过计算大网膜中每个乳斑和非乳斑部位单位面积内标记细胞的数量来量化BrdU标记细胞的分布。每只小鼠接种10⁵、10⁶和10⁷个BrdU标记的P388细胞后,乳斑部位每平方毫米分别有15.8±13.3、120±46.5和504±208个细胞,非乳斑部位每平方毫米分别有9.14×10⁻³±1.58×10⁻²、1.14×10⁻¹±7.82×10⁻²和7.07×10⁻¹±5.98×10⁻¹个细胞。乳斑部位平均标记细胞数与非乳斑部位平均标记细胞数的比值分别为1728:1、1049:1和713:1。在所有情况下,乳斑部位和非乳斑部位每平方毫米BrdU标记细胞数均有统计学显著差异。然而,随着接种细胞数量的增加,该比值下降。此外,我们给C57/BL小鼠腹腔内接种B - 16 PC黑色素瘤细胞,其因内在的黑色黑色素而易于与其他细胞区分,然后宏观和微观检查细胞的分布。还发现B - 16 PC黑色素瘤细胞也优先浸润到大网膜的乳斑中。这些结果表明,腹腔内接种的癌细胞在腹膜播散的早期阶段特异性地浸润乳斑。