class 4

Question 1

Describe the role of inflammatory chemokines in cancer progression and metastasis.

Answer 1

Inflammatory chemokines play a crucial role in cancer progression and metastasis by affecting processes such as leukocyte recruitment, angiogenesis, tumor cell survival, adhesion, proliferation, vascular permeability, immune suppression, invasion, and metastasis.

Question 2

What are some examples of inflammatory chemokines that contribute to metastasis?

Answer 2

Examples of inflammatory chemokines that contribute to metastasis include CCL2 and CCL5, which mediate the recruitment of myeloid-derived cells to metastatic sites and regulate tumor cell homing and extravasation from the circulation to distant organs.

Question 3

How do inflammatory chemokines facilitate tumor cell extravasation and metastasis?

Answer 3

Inflammatory chemokines such as CCL2 and CCL5 directly activate endothelial cells and, together with monocytes, facilitate tumor cell extravasation in a CCL2- and CCL5-dependent manner.

Question 4

Define the relationship between chronic inflammation and cancer development.

Answer 4

Chronic inflammation predisposes individuals to the development of various types of cancer, defining inflammation as a hallmark of cancer. The enhanced presence of inflammatory cells and soluble inflammatory mediators in the primary tumor is associated with poor prognosis due to metastasis.

Question 5

Describe the dual role of the immune system in cancer progression.

Answer 5

The immune system has a dual role in cancer progression, depending on the cellular context of infiltrating cells and the tumor type. This dual role can either promote or inhibit cancer progression.

Question 6

What is the significance of CX3CL1 expression in the context of metastasis?

Answer 6

CX3CL1 expression in the bone facilitates the metastasis of CX3CR1 expressing tumor cells to this site, indicating its significance in the metastatic process.

Question 7

Do inflammatory chemokines have therapeutic potential in cancer treatment?

Answer 7

Yes, current findings in preclinical models strongly suggest that inflammatory chemokines have an important role during metastasis, and targeting the chemokine axis might have therapeutic potential in cancer treatment.

Question 8

Describe the role CXCL12 and CXCR4 in breast cancer metastasis.

Answer 8

CXCL12 is the sole ligand for CXCR4, which is expressed in the bone marrow and liver. Breast cancer cells metastasize to these organs in a CXCR4-dependent manner.

Question 9

Define the role of CCR7 in melanoma metastasis to lymph nodes.

Answer 9

CCR7, another chemokine receptor, has been implicated in melanoma metastasis to lymph nodes. Its ligands, CCL19 and CCL21, are preferentially expressed in secondary lymphoid tissues.

Question 10

How is CCL19 expression in the brain essential for metastasis of CCR7-expressing T-acute lymphoblastic leukemic cells?

Answer 10

CCL19 expression by endothelial cells in the brain is essential for CCR7-expressing T-acute lymphoblastic leukemic cells to specifically seed and metastasize to the brain.

Question 11

Describe the connection between inflammatory chemokines CCL2 and CCL5 and cancer progression.

Answer 11

High levels of CCL2 and/or CCL5 have been associated with a poor outcome and shorter disease-free survival after surgery due to high incidence of metastasis in patients with breast, colon, prostate, and cervical cancer.

Question 12

Do inflammatory chemokines CCL2 and CCL5 have any predictive value in breast cancer?

Answer 12

Yes, high expression levels of CCL2 were a significant indicator of an early relapse in breast cancer. Additionally, CCL5 was found to be a predictive factor for stage II breast cancer patients.

Question 13

Describe the role of ELR-positive chemokines in angiogenesis.

Answer 13

ELR-positive chemokines, such as CXCL1, CXCL2, and CXCL8, promote angiogenesis by engaging CXCR2 on endothelial cells.

Question 14

How does CCL2 stimulate angiogenesis and chemotaxis of human microvascular endothelial cells?

Answer 14

CCL2 stimulates angiogenesis and chemotaxis of human microvascular endothelial cells by providing evidence for CCR2 expression on endothelial cells.

Question 15

Define the mechanism through which CCL2 promotes immune escape in melanoma.

Answer 15

CCL2 promotes immune escape in melanoma by recruiting monocytic CCR2-positive myeloid-derived suppressor cells to the tumor microenvironment, which in turn promotes tumor growth through immune suppression.

Question 16

What is the role of CX3CL1 in promoting angiogenesis in breast cancer?

Answer 16

CX3CL1 promotes angiogenesis in breast cancer by increasing recruitment of F4/80-positive macrophages to FGFR1-dependent breast cancer, which is dependent on CX3CL1.

Question 17

Describe the indirect effect of CCL2 on angiogenesis in prostate cancer cells.

Answer 17

CCL2 indirectly induces angiogenesis in prostate cancer cells by resulting in induced expression of proangiogenic factors like vascular endothelial growth factor (VEGF), suggesting an additional indirect effect on angiogenesis.

Question 18

Describe the role of C2 and CCL3 in tumor progression metastasis.

Answer 18

CCL2 and CCL3 recruit CD4+ and CD8+ lymphocytes and NK cells to control tumor progression and metastasis. However, their role can be complex, with CCL2 having a pro-tumorigenic activity at primary sites but inhibiting metastasis to the lungs.

Question 19

What is the impact of CCL2 deficiency on lung metastasis?

Answer 19

The deficiency of CCL2 can enhance lung metastasis.

Question 20

Define the role of neutrophils in tumor progression and metastasis.

Answer 20

Neutrophils have been suggested to have a protective anti-metastatic trait, as downregulation of CCL2 in tumor cells resulted in reduced primary tumor growth but accelerated metastasis.

Question 21

How do chemokines regulate leukocyte recruitment to metastatic sites?

Answer 21

Chemokines regulate leukocyte recruitment by forming a gradient on proteoglycans presented in the extracellular matrix or on the endothelium, which is essential for the recruitment of leukocytes to metastatic sites.

Question 22

Describe the impact of versican on metastasis.

Answer 22

Versican promotes metastasis through the enhancement of tumor-promoting inflammatory responses in the lungs and is involved in the formation of a chemokine gradient for leukocyte recruitment.

Question 23

Describe the role of CCL2 in regulating stromal-epithelial interactions in a breast cancer model.

Answer 23

CCL2 produced by cancer-associated fibroblasts regulates stromal-epithelial interactions in a breast cancer model.

Question 24

How does tumor cell-induced platelet aggregation in the circulation contribute to metastasis?

Answer 24

Tumor cell-induced platelet aggregation in the circulation promotes the arrest of metastasizing tumor cells in the vasculature and results in local endothelial activation and induced CCL5 expression.

Question 25

Define the metastatic niche and its formation.

Answer 25

The metastatic niche is formed by tumor-derived factors that enable the mobilization of bone marrow-derived cells, contributing to the formation of a pre-metastatic niche.

Question 26

What is the impact of mesenchymal stem cell-derived CCL5 production on tumor cells?

Answer 26

Mesenchymal stem cell-derived CCL5 production directly affects tumor cells, leading to a significant increase in the metastatic behavior of otherwise poorly metastatic cells.

Question 27

Describe the relationship between CCR2 inhibition and CCL2 inhibition as potential targets for cancer treatment.

Answer 27

Inhibition of CCR2 is considered a better target than inhibition of CCL2, as CCL2 is present not only within the tumor but also in the circulation in significantly larger amounts.

Question 28

What is the effect of targeted ablation of transforming growth factor-beta signaling in fibroblasts on CCL2 secretion and tumor progression?

Answer 28

Targeted ablation of transforming growth factor-beta signaling in fibroblasts results in enhanced CCL2 secretion and increased recruitment of tumor-associated macrophages, leading to an increase in tumorigenesis and metastasis.

Question 29

How does the CCL5 axis contribute to metastasis in an experimental mouse model?

Answer 29

Temporal inhibition of the CCL5 axis attenuated metastasis of both mouse and human colon carcinoma cells in an experimental metastasis mouse model.

Question 30

What is the role of endothelial CCR2 expression in the context of metastasis?

Answer 30

The dynamics of endothelial CCR2 expression not only in the lungs but also in other tissues remains to be determined in the context of metastasis.

Question 31

Describe the role of CCL2 prostate cancer metastasis to the bone.

Answer 31

CCL2 enhances migration of prostate cancer cells and mediates homing of these cells to the bone. It also stimulates osteoblastic CCL2 production in the bone microenvironment, which is required for metastatic outgrowth.

Question 32

How does CCL2 contribute to bone metastasis in prostate cancer?

Answer 32

CCL2 induces expression in the bone microenvironment, mediated by tumor-derived parathyroid hormone-related protein secretion, and promotes osteoclastogenesis. Anti-CCL2 treatment attenuates tumor growth in the bone.

Question 33

Define the role of CX3CR1 in cancer metastasis to neuronal tissues.

Answer 33

CX3CR1 expression on pancreatic and prostate cancer cells increases their invasiveness and specific metastasis to neuronal tissues. It mediates adhesion of tumor cells to the endothelium.

Question 34

What is the correlation between CX3CR1 expression and bone metastases in breast cancer?

Answer 34

Breast cancer cell line MDA-MB-231, which metastasizes to the bone, expresses significant levels of CX3CR1. In contrast, MDA-MB-436, which does not metastasize to the bone, has undetectable levels of CX3CR1.

Question 35

Describe the impact of chemokines on metastasis.

Answer 35

The contribution of chemokines to metastasis largely depends on the tissue at metastatic sites, and they play a role in mediating adhesion of tumor cells to the endothelium and promoting recruitment of myeloid cells to metastatic sites.

Question 36

Describe the role of lymphotoxin beta receptor signaling in carcinogenesis according to Wolf et al.

Answer 36

Lymphoto beta receptor signaling plays an role in carcinogenesis, from lymphoid tissue formation to the development of liver prostate cancer (Wolf et al., 2010).

Question 37

Define the multifaceted roles of chemokines in malignancy based on Ben-Baruch’s work.

Answer 37

Chemokines play diverse roles in malignancy, as outlined by Ben-Baruch, including their involvement in cancer metastasis and progression (Ben-Baruch, 2006).

Question 38

How do chemokines control leukocyte migration according to Moser et al.?

Answer 38

Moser et al. describe that chemokines exert multiple levels of control over leukocyte migration, influencing the movement of immune cells within the body (Moser et al., 2004).

Question 39

Do chemokine receptors play a role in breast cancer metastasis according to Muller et al.?

Answer 39

Yes, Muller et al. demonstrate the involvement of chemokine receptors in breast cancer metastasis, highlighting their significance in the spread of cancer cells (Muller et al., 2001).

Question 40

Describe the impact of CXC chemokine receptor-4 expression on the pulmonary metastatic potential of murine B16 melanoma cells based on Murakami et al.’s findings.

Answer 40

The expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells, as indicated by Murakami et al. (Murakami et al., 2002).

Question 41

Define the multigenic program mediating breast cancer metastasis to bone according to Kang et al.

Answer 41

Kang et al. describe a multigenic program that mediates breast cancer metastasis to bone, shedding light on the genetic factors involved in this process (Kang et al., 2003).

Question 42

How do CXCR4 and CXCL12 participate in the extravasation of metastasizing breast cancer cells within the liver according to Wendel et al.?

Answer 42

Wendel et al. demonstrate that CXCR4 and CXCL12 participate in the extravasation of metastasizing breast cancer cells within the liver, highlighting their role in the spread of cancer to this organ (Wendel et al., 2012).

Question 43

Describe the significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer according to Ueno et al.

Answer 43

Ueno et al. emphasize the significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer, underscoring its role in the tumor microenvironment (Ueno et al., 2000).

Question 44

Describe the role of MCP-1 and MIP-1 in regulating protective anti-tumor immunity to localized and metastatic B16 melanoma.

Answer 44

These host-derived factors regulate protective anti-tumor immunity to B16 melanoma.

Question 45

What is the impact of TGF-beta on the polarization of tumor-associated neutrophil phenotype?

Answer 45

TGF-beta polarizes the phenotype into ‘N1’ versus ‘N2’ TAN.

Question 46

Define the role of granulocyte-colony stimulating factor in promoting lung metastasis.

Answer 46

It promotes lung metastasis through mobilization of specific granulocytes.

Question 47

How does RhoGDI2 suppress lung metastasis in mice?

Answer 47

It does so by reducing tumor versican expression and macrophage infiltration.

Question 48

Describe the mechanism by which Chemokine (C-C motif) ligand 2 promotes breast cancer metastasis to lung and bone.

Answer 48

It engages stromal cells of monocytic origin to promote metastasis.

Question 49

What is the function of a chemokine receptor antagonist in inhibiting experimental breast tumor growth?

Answer 49

It inhibits experimental breast tumor growth.

Question 50

Do CCL2 recruit inflammatory monocytes to facilitate breast-tumor metastasis?

Answer 50

Yes, CCL2 recruits inflammatory monocytes to facilitate breast-tumor metastasis.