Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome
Abstract
A patient with adrenocortical carcinoma presented with fever, leukocytosis, and increased acute phase reactants. The tumor was infiltrated with neutrophils. Immunohistochemical staining of the tumor showed positive signal for epithelial neutrophil-activating protein-78, an angiogenic and chemotactic CXC chemokine. Conditioned medium from tumor-derived cells (RL-251) showed high concentration of IL-8, epithelial neutrophil-activating protein-78, Gro alpha, and Gro gamma, angiogenic CXC chemokines with a potential role in tumorigenesis. An adrenal cancer/severe combined immunodeficiency mouse chimera was developed. Mice grew tumors rapidly, and circulating levels of IL-8 and epithelial neutrophil-activating protein-78 were detected. In contrast, animals transplanted with NCI-H295 cells, a nonchemokine-secreting cell line, grew tumors more slowly and did not have detectable chemokine levels. Similar to the patient, mice with RL-251 tumors developed marked leukocytosis and neutrophilia, and their tumors were infiltrated with neutrophils. Mice were passively immunized with epithelial neutrophil-activating protein-78 antisera. A marked decrease in tumor growth was observed. Potential for chemokine production by other adrenocortical tumors was investigated by RT-PCR in archival material. Six of seven adrenal carcinomas and one of three adenomas had cDNA for IL-8; six of seven carcinomas and the three adenomas had cDNA for epithelial neutrophil-activating protein-78. We concluded that the clinical presentation of this case resulted from increased tumor production of chemotactic chemokines. Through their angiogenic and chemotactic properties these chemokines may play an important role in adrenal tumorigenesis.
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Adrenocortical carcinomas are retroperitoneal and may present late, often having reached a large size.
“As ACCs are retroperitoneal they may present late and have often reached a large size (131).”
From Adrenal incidentaloma (2020) · cites this paper as [131]
Other rare paraneoplastic syndromes are hyperreninemic hyperaldosteronism, erythropoietin-associated polycythemia, and leukocytosis (caused by chemokine release from the tumor).
“Other rare paraneoplastic syndromes are hyperreninemic hyperaldosteronism, erythropoietin-associated polycythemia, and leukocytosis (caused by chemokine release from the tumor) (82–84).”
From Adrenocortical carcinoma (2014) · cites this paper as [84]
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- Authors
- Schteingart, D. E., Giordano, T. J., Benitez, R. S., Burdick, M. D., Starkman, M. N., Arenberg, D. A., & Strieter, R. M.
- Affiliations
- University of Michigan (US)
- Pathology (T.J.G.), Ann Arbor, Michigan 48109
- University of California, Los Angeles (US)
- Corresponding author
- Schteingart, David E.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2001-08-01
- Volume
- 86
- Issue
- 8
- Pages
- 3968-3974
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2141837648
- Cited by
- 45
- References
- 27
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2013: 2 · 2012: 3
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL66027, R01HL066027)
- National Cancer Institute (CA-87879, R01CA087879)
- National Center for Research Resources (NCRR-M-01-RR-000-42)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Keywords
- adrenocortical carcinoma, CXC chemokines, interleukin-8, neutrophil infiltration, leukocytosis, fever, acute phase proteins, tumor angiogenesis, tumor growth, adrenal adenoma
- MeSH terms
- Adenoma, Adrenal Cortex Neoplasms, Adrenocorticotropic Hormone, Aged, Circadian Rhythm, Fever, Humans, Hydrocortisone, Immunohistochemistry, Leukocytosis, Male, Neutrophils, Syndrome, Tumor Cells, Cultured, 17-Hydroxycorticosteroids, 17-Ketosteroids, Interleukin-8, Neutrophil Activation, Chemokines, CXC, Reverse Transcriptase Polymerase Chain Reaction, Chemokine CXCL5
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