AntiCancer, Inc., San Diego, California, USA.
J Cell Biochem. 2011 Dec;112(12):3549-54. doi: 10.1002/jcb.23282.
We report here that XPA1 human pancreatic cancer cells are dimorphic. After injection in the spleen, XPA1 cells isolated from the primary tumor in the spleen were predominantly round; while cells isolated from the resulting liver metastasis and ascites were comprised of both round- and spindle-shaped cell types. Cancer cells previously grown in the spleen and re-implanted in the spleen developed large primary tumors in the spleen only. Cancer cells isolated from liver metastasis and re-transplanted to the spleen resulted in a primary tumor in the spleen and liver metastasis. Cancer cells derived from ascites and re-transplanted to the spleen developed primary tumors in the spleen and distant metastasis in the liver, lung, and diaphragm in addition to ascites formation. Spindle and round cells were differentially labeled with fluorescent proteins of different colors. After co-injection of the two cell types in the spleen, cells were isolated from the primary tumors, liver metastasis, and ascites and analyzed by color-coded fluorescence microscopy and fluorescence-activated cell sorting (FACS). No significant differences between the percentages of spindle-shaped and round cancer cells in the primary tumor and the liver metastasis were observed. However, spindle-shaped cancer cells were enriched in the ascites. One hundred percent of the spindle-shaped and round cancer cells expressed CD44, suggesting that morphology and metastatic behavior rather than CD44 expression can distinguish the stem-like cells of the XPA1 pancreatic cancer cell line. The spindle-shaped cancer cells had the greater capability for distant metastasis and ascites formation, suggesting they are stem-like cells, which can be readily targeted for therapy.
我们在此报告，XPA1 人胰腺癌细胞是二态性的。在脾脏注射后，从脾脏原发性肿瘤中分离出的 XPA1 细胞主要呈圆形；而从继发的肝转移和腹水分离出的细胞则由圆形和纺锤形细胞类型组成。以前在脾脏中生长并重新植入脾脏的癌细胞仅在脾脏中形成大的原发性肿瘤。从肝转移中分离出并重新移植到脾脏的癌细胞导致脾脏原发性肿瘤和肝转移。源自腹水并重新移植到脾脏的癌细胞在脾脏和肝脏中形成原发性肿瘤，并在肺部和横膈膜形成远处转移，此外还伴有腹水形成。纺锤形和圆形细胞用不同颜色的荧光蛋白进行了差异标记。将两种细胞类型共同注射到脾脏后，从原发性肿瘤、肝转移和腹水中分离出细胞，并通过彩色荧光显微镜和荧光激活细胞分选（FACS）进行分析。在原发性肿瘤和肝转移中，纺锤形和圆形癌细胞的比例没有显著差异。然而，纺锤形癌细胞在腹水中富集。100%的纺锤形和圆形癌细胞表达 CD44，表明形态和转移行为而不是 CD44 表达可以区分 XPA1 胰腺癌细胞系的干细胞样细胞。纺锤形癌细胞具有更强的远处转移和腹水形成能力，表明它们是干细胞样细胞，可作为治疗的靶点。
