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Secretion of basement membrane collagen degrading enzyme and plasminogen activator by transformed cells – role in metastasis
Author(s) -
Salo Tuula,
Liotta Lance A.,
KeskiOja Jorma,
TurpeenniemiHujanen Taina,
Tryggvason Karl
Publication year - 1982
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/ijc.2910300520
Subject(s) - plasmin , collagenase , plasminogen activator , secretion , microbial collagenase , basement membrane , cell culture , enzyme , fibrosarcoma , microbiology and biotechnology , chemistry , biology , biochemistry , endocrinology , genetics
The relationship of a basement membrane collagen degrading enzyme (BM collagenase) and plasminogen activator (PA) was studied in a number of non‐malignant and malignant human and murine cell lines. Several non‐malignant cell lines secreted significant amounts of PA but no detectable BM collagenase activity whereas the malignant cell lines, with one exception, secreted both enzymes. Therefore, the secretion of BM collagenase appears to be a characteristic of many malignant cells whereas PA is synthesized also by normal cells. The BM collagenase needed proteolytic activation for maximal activity indicating that it is secreted in a latent form. The addition of plasminogen to the culture medium of human fibrosarcoma cells (HT‐1080) resulted in maximal activation of the enzyme. Plasmin, but not plasminogen, increased the activity of partially purified enzyme protein. Accordingly, the activation of latent BM collagenase in vivo may be facilitated by PA through the conversion of plasminogen to plasmin. It is suggested that the secretion of BM collagenase concomtantly with PA is a prerequisite for metastasis.