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The source of APRIL up‐regulation in human solid tumor lesions
Author(s) -
MhawechFauceglia P.,
Kaya G.,
Sauter G.,
McKee T.,
Donze O.,
Schwaller J.,
Huard B.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1105655
Subject(s) - biology , stroma , melanoma , pathology , cancer research , tumor necrosis factor alpha , in situ hybridization , tumor microenvironment , carcinoma in situ , cancer , immunohistochemistry , messenger rna , tumor cells , immunology , gene , medicine , biochemistry , genetics
Abundant mRNA expression for a proliferation‐inducing ligand (APRIL) from tumor necrosis factor (TNF) family is observed in many solid tumors. Here, we analyzed in situ the cellular source of APRIL in human solid tumors with anti‐APRIL antibodies. In most cases, neutrophils present in the tumor stroma constituted the main source of APRIL. In cutaneous lesions such as melanoma or basal cell carcinoma, tumor‐adjacent keratinocytes also produced APRIL. APRIL production by tumor cells themselves was a rare event, only observed in urothelial bladder cancer and squamous cell carcinoma. Detailed analysis revealed that APRIL dissociated from producing cells, and secreted APRIL was retained in the tumor lesions. A direct binding onto tumor cells via heparan sulfate proteoglycans (HSPG) was observed in in vitro experiments and confirmed in situ. Taken together, our analysis indicates a potential role for HSPG/APRIL interactions in the development of solid tumors.