Up-regulation of Muc4 and its complex formation with ErbB2 in murine gallbladder carcinomaȁa potential mechanism for gallbladder carcinogenesis and/or tumor growth

Abstract

mphoid cells increased in the medulla during 24 to 48 h. The number of cax~cer cells in the marginal sinus reached the maximmu at 6 h, then declined until 48 h, but significant proliferation was observed front 4 days atier inoculation. The marginal sinus was then filled with cancer cells and expanded. At this period, the ED3 macrophages accumulated and intermingled with cancer ceils, Some cancer ceils resulted in apoptosis, being incorporated by the ED3 macrophages. In LN depleted of macrophages with liposomes containing DMDP, cancer cells massivdy invade the LN parenchyma TNF-e~ and IL-I[3 in the LN significanfly increased at ] and 3 h, respectively [1-2 increased significantly during 6 to 24 h. These cytokines returned to the basal level thereaher. 1FN-y or IL-12 did not increase at earlier periods, but significantly decreased from 24 to 96 h Localization of IL113 positive cells was consistent with that of ED2 macrophage in the medulla, but not of ED3 macrophage. TNF-cx positive cells were found in the germinal centen Conclusions: Immune responses in thks study include germinal center activation, followed by lymphoid cell pmlileration in the medulla and sinus histiocytosis, which mimic histological maniIestations of regional LN in cancer patients with improved survival Thus, LN did have capability to eliminate carmer cells temporarily. Depiction of immunocompetent cells due to deterioranon of cytokine induction may be responsible for later loss of the capabihty to prevent metastasis Macmphages contribute as a first line defense against cancer invasion. There is a different role in preventing metastasis between marginal atrd medullary sinus macrophages.