We showed in previous work that LAK cell supernatants contain a large molecular weight factor with toxic activity for A375 melanoma and other cell lines. The factor, Fr1, was identified tentatively as TGFβrelated, since its activity was abolished by anti-TGFβ serum. This relatedness is further confirmed in the present work, which demonstrates that, like TGFβ Fr1 stimulates the release and deposition of fibronectin and induces morphological changes indistinguishable from those induced by TGFβ The TGFβ derived from LAK cells, although associated with a large carrier molecule, is directly acting and does not dissociate from its carrier following gel filtration in acetic acid. Its carrier is different from alpha-2 macroglobulin. SDS-PAGE and immunoblotting showed that FR1 contains TGFβ complexed with large molecules (150 and <200 kDa), which dissociate in reduced gels to molecules of 60-67 kDa. We interpret these data as showing that TGFβ secreted by LAK cells is, presumably, covalently linked to monomeric carrier molecules of approximately 60 kDa, which, in turn, are S-S bonded to form multimeric molecules of 150 kDa and <200 kDa.
Bibliographical noteFunding Information:
We gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles, and the Wakefern/ShopRite Endowment for Basic Research in Cancer Biology and Immunology. We are greatly indebted to Dr A. Roberts for reading the manuscript and for her valuable suggestions. We also thank Prof J. Vaage for a gift of IL-2, Prof David Weiss for his sup- port and encouragement, and Ms Inbal Heth and Marcella Wachtel for assistance in the preparation of this manuscript.
- LAK cells
- TGFβ carrier
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology