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Human breast‐cancer metastasis formation in a nude‐mouse model: Studies of hyaluronidase, hyaluronan and hyaluronan‐binding sites in metastatic cells
Author(s) -
Victor Régine,
Chauzy Claude,
Girard Nicole,
Gioanni Jeanine,
d'Anjou Joëlle,
Stora De Novion Hélène,
Delpech Bertrand
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990702)82:1<77::aid-ijc14>3.0.co;2-q
Subject(s) - metastasis , cd44 , nude mouse , pathology , hyaluronidase , cell culture , hyaluronic acid , cancer research , stroma , cancer , immunohistochemistry , biology , medicine , cell , anatomy , biochemistry , genetics , enzyme
Few animal models are available to study metastasis formation. The purpose of the present study was to obtain a useful model of metastasis formation in nude mice in an attempt to analyze the stroma reaction and in particular the production and the expression of hyaluronan (HA), hyaluronidase, and HA‐binding sites by cultivated cells, and HA and hyaluronectin (HN) in the invasive areas of tumors. Nude mice were subjected to i.p. injections of several human cancer cell lines (PLC/PRF/5, HepG2, CB 191, CB 193, PC3, CAL 51, SA 87 and SA 98), and formation of metastases was analyzed in different organs (lung, liver, kidney, spleen and axillary nodes) by immunohistochemical techniques. CAL 51, a breast‐cancer‐metastasis‐derived cell line with a normal karyotype, produced i.p. tumors in 75% animals and metastases in 90% animals (detected in the liver and axillary nodes). Two modes of invasion by CAL 51 cells were observed in the liver: one, direct, from the surface of the liver and the other, indirect, via the bloodstream. HA and HN were strongly expressed at the invasion areas. A cell line derived from hepatic metastasis of CAL 51 (HMD CAL 51) presented an abnormal karyotype. HMD CAL 51 produced more hyaluronidase (12‐fold) and HA (10‐fold) and expressed more CD44 (1.6‐fold) and other HA‐binding sites (9.5‐fold) than the established cell line CAL 51. Our results show that i.p. injection of the CAL 51 cell line into nude mice provides a useful model of metastasis formation. The passage of the CAL 51 cells from the primary state to the metastatic state was characterized by a dramatic increase of HA and hyaluronidase production, and expression of HA, HN and HA‐binding sites. Int. J. Cancer 82:77–83, 1999. © 1999 Wiley‐Liss, Inc.