Establishment and characterization of two new rectal neuroendocrine cell carcinoma cell lines.
BACKGROUND
Human colorectal neuroendocrine cell carcinoma (NEC) is a rare disease with a poor prognosis. The biological behavior of NEC remains poorly understood.


METHODS
We established two new NEC cell lines from a patient with rectal neuroendocrine carcinoma, NECS-P and NECS-L from the primary tumor and a liver metastasis, respectively. We investigated the biological differences between the two cell lines to study the mechanisms involved in liver metastasis.


RESULTS
There was no difference between NECS-P and NECS-L in the morphological, ultrastructural and immunohistochemical studies. After addition of TGF-beta(1), the doubling times of NECS-P were increased in a dose-dependent manner relative to untreated cells, whereas TGF-beta(1) had no effect on NECS-L. The attachment and chemotactic response of the two cell lines were not enhanced by TGF-beta(1). The invasive capacity and the production of matrix metalloproteinase-2 (MMP-2) were significantly increased only in NECS-L following the addition of TGF-beta(1). When anti-MMP-2 antibody was added to the medium with TGF-beta(1), NECS-L invasion was inhibited.


CONCLUSIONS
It is considered that these differences are important to understand the mechanisms of liver metastasis of NEC.
Takahashi
Y
Y
First Department of Surgery, Nippon Medical School, Tokyo, Japan. yyr@mbe.sphere.ne.jp
Onda
M
M
Tanaka
N
N
Seya
T
T
D018278:Carcinoma, Neuroendocrine / Q000556:secondary*; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D012004:Rectal Neoplasms / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1