Association of spleen-derived stem-like cells with hematogenous metastasis development

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Abstract

BACKGROUND: Spleen status has been associated with survival in patients with carcinoma, potentially mediated by the effects of immunosuppressive hematopoietic cells in the spleen.

AIM: This study aimed to investigate the composition and quantity of hematopoietic stem-like cells in the spleen and their relationship with hematogenous metastases in patients with varying carcinoma types.

MATERIAL AND METHODS: Forty patients with carcinomas of the stomach, gastroesophageal junction, pancreas, splenic flexure of the colon, sigmoid colon, kidney, ovary, and uterus were examined. The subgroup with hematogenous metastases (15 patients) included 7 cases of gastric cancer, 1 of gastroesophageal junction cancer, 4 of colon cancer, 1 of pancreatic cancer, 1 of renal cancer, and 1 of ovarian cancer. The subgroup without hematogenous metastases (13 patients) comprised 6 cases of gastric cancer, 4 of gastroesophageal junction cancer, 1 of colon cancer, 1 of pancreatic cancer, and 1 of uterine cancer. Formalin-fixed, paraffin-embedded spleen tissue sections were analyzed using multiplex tyramide signal amplification, a modified immunohistochemistry technique, with antibodies to CD45, CD34, CD133, TIE2, VEGFR1, CD90, and CD11b. Data are presented as median (Me) and interquartile range (Q1–Q3). Differences between groups were assessed using the Mann–Whitney U test. ROC analysis was employed to evaluate the prognostic significance of the parameters. P < 0.05 indicated significant differences.

RESULTS: Multiparametric analysis of spleen tissue identified 20 phenotypes within the continuum of hematopoietic stem cells and cells with hematopoietic/angiogenic potential, exhibiting phenotypic diversity. Across all carcinoma types, the number of CD45–CD34+CD133–TIE2–VEGFR1– stem-like cells in lymphoid follicles was lower in patients with hematogenous metastases: 43.313 (0.00–85.393) and 110.034 (83.050–197.915), respectively (p = 0.03). The number of stem-like cells with the CD45–CD34+CD133–TIE2–VEGFR1– phenotype was lower in the group of patients with gastric cancer and hematogenous metastases (31.092 [0.000–37.987]) than in the group without hematogenous metastases (119.962 [103.486–258.533]) (p = 0.001). In contrast, the number of hematopoietic progenitor cells with the CD45+CD34–CD133+TIE2–VEGFR1– phenotype identified in the lymphoid follicle was higher (7901.164 [5705.314–8563.807] vs 4670.894 [3328.607–6473.649]) (p = 0.035), as well as the number of CD45+CD34–CD133+TIE2+VEGFR1+ cells detected in the red pulp of the spleen (131.396 [35.701–167.521] vs 21.524 [6.123–30.117]) (p = 0.02).

CONCLUSION: The number of spleen-derived cells with the phenotypes CD45–CD34+CD133–TIE2–VEGFR1–, CD45+CD34–CD133+TIE2–VEGFR1–, and CD45+CD34–CD133+TIE2+VEGFR1+ is associated with hematogenous metastasis.

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About the authors

Elena S. Andryukhova

Tomsk National Research Medical Center, Russian Academy of Sciences

Author for correspondence.
Email: elenasergeevna9607@gmail.com
ORCID iD: 0000-0003-0909-9206
SPIN-code: 3565-7265

Junior Researcher, Depart. of General and Molecular Pathology, Oncology Research Institute

Russian Federation, Tomsk

Lyubov A. Tashireva

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: tashireva@oncology.tomsk.ru
ORCID iD: 0000-0003-2061-8417
SPIN-code: 4371-5340

MD, Dr. Sci. (Med.), Head of the Laboratory, Laboratory of Molecular Cancer Therapy, Oncology Research Institute

Russian Federation, Tomsk

Sergey G. Afanasyev

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: doc1966@yandex.ru
ORCID iD: 0000-0002-4701-0375
SPIN-code: 9206-3037

MD, Dr. Sci. (Med.), Prof., Head of Depart., Depart. of Abdominal Oncology, Oncology Research Institute

Russian Federation, Tomsk

Marina V. Zavyalova

Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical University

Email: zavyalovamv@mail.ru
ORCID iD: 0000-0001-9429-9813
SPIN-code: 1229-0323

MD, Dr. Sci. (Med.), Prof., Leading Researcher, Depart. of General and Molecular Pathology, Oncology Research Institute; Head of Depart., Depart. Of Pathology

Russian Federation, Tomsk; Tomsk

Vladimir M. Perelmuter

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: pvmngs@yandex.ru
ORCID iD: 0000-0002-7633-9620
SPIN-code: 6252-5319

MD, Dr. Sci. (Med.), Prof., Honored Scientist of the Russian Federation, Chief Researcher, Depart. of General and Molecular Pathology, Oncology Research Institute

Russian Federation, Tomsk

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2. Fig. 1. Tyramide signal amplification method—modified multicolor immunofluorescent staining of splenic red pulp. Pink arrow: CD45–CD34+CD133–TIE2–VEGFR1– (No. 2); yellow arrow: CD45+CD34–CD133+TIE2–VEGFR1– (No. 8).

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3. Fig. 2. Tyramide signal amplification method—modified multicolor immunofluorescent staining of splenic red pulp. White arrow: CD45+CD34–CD133+TIE2+VEGFR1+ (No. 16).

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4. Fig. 3. Correlation patterns among stem-like cells in the splenic red pulp: a, group without hematogenous metastases; b, group with hematogenous metastases. Correlation coefficients and directions for each phenotype pair are indicated. Red: negative correlations; blue: positive correlations.

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