Association of spleen cells with stem cell traits with the development of hematogenous metastases

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Abstract

BACKGROUND: Spleen status is associated with survival in carcinomas. One of the mechanisms may be related to the effects of immunosuppressive hematopoietic cells originating from the spleen.

AIM: To study the composition and quantity of hematopoietic cells with stem cell traits in the spleen and their association with hematogenous metastasis in patients with different nosological forms of carcinomas.

MATERIAL AND METHODS: The study included 40 patients with stomach cancer, cardioesophageal junction cancer, cancer of pancreas, splenic flexure of the colon, sigmoid colon, kidney, ovary and uterus. The subgroup with hematogenous metastases (15 patients) included 7 cases of stomach cancer, 1 case of cardioesophageal junction cancer, 4 cases of colon cancer, 1 case of pancreatic cancer, 1 case of kidney cancer, and 1 case of ovarian cancer. The subgroup without hematogenous metastases (13 patients) included 6 cases of stomach cancer, 4 cases of cardioesophageal junction cancer, 1 case of colon cancer, 1 case of pancreatic cancer, and 1 case of uterine cancer. Formalin-fixed and paraffin-embedded spleen tissue sections served as the study material. The method of multiplex tyramide signal amplification — modified immunohistochemistry of tissue sections was applied, using antibodies to CD45, CD34, CD133, TIE2, VEGFR1, CD90, CD11b. The studied parameters were described as median (Me) and interquartile range (Q1–Q3). Differences in parameters were assessed using the Mann–Whitney criterion. ROC analysis was used to assess the prognostic value of the parameters. Differences were considered significant at a significance level of p <0.05.

RESULTS: The study of spleen tissue with simultaneous determination of several markers on each cell allowed us to identify 20 phenotypes related to representatives of the continuum of hematopoietic stem cells and the continuum of stem cells with hematopoietic/angiogenic potentials, characterized by pronounced phenotypic diversity. In the general group, including all the studied nosological forms, the number of stem cells with the CD45–CD34+CD133–TIE2–VEGFR1– phenotype found in the lymphoid follicles of the spleen was lower in cases with hematogenous metastases: 43.313 (0.00–85.393) and 110.034 (83.050–197.915) (p=0.03), respectively. In the group of gastric cancer patients with hematogenous metastases, a lower number of stem cells with the CD45–CD34+CD133–TIE2–VEGFR1– phenotype [31.092 (0.000–37.987)] compared to the group without hematogenous metastases [119.962 (103.486–258.533)] (p=0.001), a higher number of stem progenitor cells with the CD45+CD34–CD133+TIE2–VEGFR1– phenotype determined in the lymphoid follicle [7901.164 (5705.314–8563.807) versus 4670.894 (3328.607–6473.649)] (p=0.035), as well as a higher number of cells with phenotype CD45+CD34–CD133+TIE2+VEGFR1+, identified in the red pulp of the spleen [131.396 (35.701–167.521) versus 21.524 (6.123–30.117)] (p=0.02), were found.

CONCLUSION: The number of spleen 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 assay — modified multicolor immunofluorescence staining of red pulp of the spleen. 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 assay — a modified multicolor immunofluorescent staining of red pulp of the spleen. White arrow — CD45+CD34–CD133+TIE2+VEGFR1+ (No. 16)

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4. Fig. 3. Correlation relationships between cells with stem cell traits in the red pulp of the spleen: a — a group of patients without hematogenous metastases; b — a group of patients with hematogenous metastases. The correlation coefficients and signs are indicated for each pair of phenotypes. Negative values of the correlation coefficients are shown in red, positive values — in blue

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