Heterogeneity in the production of collagens and fibronectin by morphologically distinct clones of a human tumor cell line: evidence for intratumoral diversity in matrix protein biosynthesis.
Recent studies of murine tumor models and certain human tumor cell lines have provided evidence for intratumor heterogeneity in expression of extracellular matrix receptors and in the elaboration of matrix-degrading enzymes. However, little is known about possible intratumoral heterogeneity in the production of matrix macromolecules. We have, therefore, examined the biosynthesis and secretion of matrix proteins by cells derived from a polyclonal human cell line (JH-17) established from a large cell undifferentiated carcinoma of the lung. For the present studies, we focused on the production of collagens and structural glycoproteins by two phenotypically different aneuploid clones, designated C13 and C22. These clones were distinctive in their inability to grow in soft agar or to form tumors in nude mice and had identical DNA contents. Tumor cells were labeled with [3H]proline and the newly synthesized proteins accumulating in the culture medium were identified using biochemical and immunologic techniques. Clone C13 secreted at least three genetically distinct collagens, including type V procollagen (PC), type IV procollagen, and a type VIII-like collagen. By contrast, the clone C22 synthesized fibronectin, and a single bacterial collagenase-sensitive and pepsin-resistant component consistent with type I trimer. These studies emphasize the potential diversity of matrix proteins synthesized by neoplastic cells and suggest that there is intratumoral heterogeneity in matrix protein biosynthesis in vivo. These studies further suggest that tumor-derived matrix may be altered during tumor progression or cell selection in vivo.
Crouch
E C
EC
Department of Pathology, Jewish Hospital at Washington University Medical Center, St. Louis, Missouri 63110.
Stone
K R
KR
Bloch
M
M
McDivitt
R W
RW
D018288:Carcinoma, Small Cell / Q000473:pathology; D002460:Cell Line; D002999:Clone Cells; D003094:Collagen / Q000096:biosynthesis* / Q000302:isolation & purification; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis* / Q000302:isolation & purification; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology
D005353:Fibronectins; D003094:Collagen