Hohn H P, Linke M, Ugele B, Denker H W
Universitätsklinikum, Universität-GH Essen, Essen, Germany.
Exp Cell Res. 1998 Oct 10;244(1):249-58. doi: 10.1006/excr.1998.4184.
In tumor cells, malignant (invasive) behavior and differentiation tend to be correlated inversely, although it is not clear to what extent this can be generalized and whether it may also apply to normal invasive cell types. We have modulated differentiation of normal trophoblast cells from first trimester or term placenta as well as choriocarcinoma cells (BeWo, Jeg-3, and JAr) with retinoic acid (RA), methotrexate (MTX), dibutyryl-cAMP (dbcAMP), or phorbol-[12-myristoyl-13-acetyl]-diester (PMA). The secretion of the differentiation marker chorionic gonadotrophin was stimulated by nearly all substances in all cell types. The activity of cellular sterylsulfatase showed a tendency to be increased (decreased by RA and dbcAMP in normal trophoblast; not detected in JAr). Invasiveness was decreased by all effectors in normal trophoblast (both types) and in BeWo. In Jeg-3 and JAr, however, PMA treatment (in JAr also RA treatment) increased invasion rates. These results suggest that only in normal trophoblast and in BeWo (but not in other choriocarcinoma cells, i.e., Jeg-3 and JAr) invasiveness and differentiation tend to be correlated inversely. When extrapolating to the various subpopulations of cells within a tumor, induction of differentiation-as intended in certain strategies for tumor therapy ("differentiation therapy")-may have the unwanted effect of stimulating invasiveness in certain subpopulations of tumor cells.
在肿瘤细胞中，恶性（侵袭性）行为与分化往往呈负相关，尽管尚不清楚这种相关性在多大程度上具有普遍性，以及是否也适用于正常的侵袭性细胞类型。我们用视黄酸（RA）、甲氨蝶呤（MTX）、二丁酰环磷腺苷（dbcAMP）或佛波醇[12-肉豆蔻酰-13-乙酰]酯（PMA）调节了来自孕早期或足月胎盘的正常滋养层细胞以及绒毛膜癌细胞（BeWo、Jeg-3和JAr）的分化。几乎所有物质在所有细胞类型中均刺激了分化标志物绒毛膜促性腺激素的分泌。细胞甾醇硫酸酯酶的活性呈增加趋势（在正常滋养层细胞中，RA和dbcAMP使其降低；在JAr细胞中未检测到）。在正常滋养层细胞（两种类型）和BeWo细胞中，所有效应物均降低了侵袭性。然而，在Jeg-3和JAr细胞中，PMA处理（在JAr细胞中RA处理也）增加了侵袭率。这些结果表明，仅在正常滋养层细胞和BeWo细胞中（而非在其他绒毛膜癌细胞，即Jeg-3和JAr细胞中），侵袭性与分化往往呈负相关。当推断肿瘤内的各种细胞亚群时，如某些肿瘤治疗策略（“分化治疗”）中所期望的那样诱导分化，可能会在某些肿瘤细胞亚群中产生刺激侵袭性的不良效果。
